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Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.
Zhu, G; Wang, Y; Li, J; Wang, J
Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. PMID:25724866
Ginsenoside Rg1 enhances lymphatic transport of intrapulmonary silica via VEGF-C/VEGFR-3 signaling in silicotic rats.
Yu, Jie; Mao, Lijun; Guan, Li; Zhang, Yanlin; Zhao, Jinyuan
Ginsenoside Rg1, extracted mainly from Panax ginseng, has been shown to exert strong pro-angiogenic activities in vivo. But it is unclear whether ginsenoside Rg1 could promote lung lymphangiogenesis to improve lymphatic transport of intrapulmonary silica in silicotic rats. Here we investigated the effect of ginsenoside Rg1 on lymphatic transport of silica during experimental silicosis, and found that ginsenoside Rg1 treatment significantly raised the silicon content in tracheobronchial lymph nodes and serum to reduce the silicon level in lung interstitium, meanwhile increased pulmonary lymphatic vessel density by enhancing the protein and mRNA expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3). The stimulative effect of ginsenoside Rg1 on lymphatic transport of silica was actively correlated with its pro-lymphangiogenic identity. And VEGFR-3 inhibitor SAR131675 blocked these above effects of ginsenoside Rg1. These findings suggest that ginsenoside Rg1 exhibits good protective effect against lung burden of silica during experimental silicosis through improving lymphatic transport of intrapulmonary silica, which is potentially associated with the activation of VEGF-C/VEGFR-3 signaling pathway. PMID:26920056
Ginsenoside Rg1 promotes osteogenic differentiation of rBMSCs and healing of rat tibial fractures through regulation of GR-dependent BMP-2/SMAD signaling.
Gu, Yanqing; Zhou, Jinchun; Wang, Qin; Fan, Weimin; Yin, Guoyong
Fracture healing is closely related to the number and activity of bone marrow mesenchymal stem cells (BMSCs) near the fracture site. The present study was to investigate the effect of Rg1 on osteogenic differentiation of cultured BMSCs and related mechanisms and on the fracture healing in a fracture model. In vitro experiments showed that Rg1 promoted the proliferation and osteogenic differentiation of BMSCs. Western blot analyses demonstrated that Rg1 promoted osteogenic differentiation of BMSCs through the glucocorticoid receptor (GR)-dependent BMP-2/Smad signaling pathway. In vivo, X-ray examination showed that callus growth in rats treated with Rg1 was substantially faster than that in control rats after fracture. The results of H&E and Safranin-O/Fast Green staining revealed that, compared with controls, rats in the Rg1 treatment group had a significantly higher proportion of trabecular bone but a much lower proportion of fibers and cartilage components inside the callus. Micro-CT suggested that bone mineral density (BMD), percent bone volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly increased in the treatment group, whereas trabecular separation (Tb.Sp) was significantly reduced. Thus, Rg1 promotes osteogenic differentiation by activating the GR/BMP-2 signaling pathway, enhances bone calcification, and ultimately accelerates the fracture healing in rats. PMID:27141994
Ginsenoside Rg1 promotes osteogenic differentiation of rBMSCs and healing of rat tibial fractures through regulation of GR-dependent BMP-2/SMAD signaling
Gu, Yanqing; Zhou, Jinchun; Wang, Qin; Fan, Weimin; Yin, Guoyong
Fracture healing is closely related to the number and activity of bone marrow mesenchymal stem cells (BMSCs) near the fracture site. The present study was to investigate the effect of Rg1 on osteogenic differentiation of cultured BMSCs and related mechanisms and on the fracture healing in a fracture model. In vitro experiments showed that Rg1 promoted the proliferation and osteogenic differentiation of BMSCs. Western blot analyses demonstrated that Rg1 promoted osteogenic differentiation of BMSCs through the glucocorticoid receptor (GR)-dependent BMP-2/Smad signaling pathway. In vivo, X-ray examination showed that callus growth in rats treated with Rg1 was substantially faster than that in control rats after fracture. The results of H&E and Safranin-O/Fast Green staining revealed that, compared with controls, rats in the Rg1 treatment group had a significantly higher proportion of trabecular bone but a much lower proportion of fibers and cartilage components inside the callus. Micro-CT suggested that bone mineral density (BMD), percent bone volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly increased in the treatment group, whereas trabecular separation (Tb.Sp) was significantly reduced. Thus, Rg1 promotes osteogenic differentiation by activating the GR/BMP-2 signaling pathway, enhances bone calcification, and ultimately accelerates the fracture healing in rats. PMID:27141994
Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer's disease model.
Li, Fengling; Wu, Xiqing; Li, Jing; Niu, Qingliang
The complex etiopathogenesis of Alzheimer's disease (AD) has limited progression in the identification of effective therapeutic agents. Amyloid precursor protein (APP) and presenilin‑1 (PS1) are always overexpressed in AD, and are considered to be the initiators of the formation of β‑amyloid plaques and the symptoms of AD. In the present study, a transgenic AD model, constructed via the overexpression of APP and PS1, was used to verify the protective effects of ginsenoside Rg1 on memory performance and synaptic plasticity. AD mice (6‑month‑old) were treated via intraperitoneal injection of 0.1‑10 mg/kg ginsenoside Rg1. Long‑term memory, synaptic plasticity, and the levels of AD‑associated and synaptic plasticity‑associated proteins were measured following treatment. Memory was measured using a fear conditioning task and protein expression levels were investigated using western blotting. All the data was analyzed by one-way analysis of variance or t‑test. Following 30 days of consecutive treatment, memory in the AD mouse model was ameliorated in the 10 mg/kg ginsenoside Rg1 treatment group. As demonstrated by biochemical experiments, ginsenoside Rg1 treatment reduced the accumulations of β‑amyloid 1‑42 and phosphorylated (p)‑Tau in the AD model. Additionally, brain-derived neurotrophic factor (BDNF) and p‑TrkB synaptic plasticity‑associated proteins were upregulated following ginsenoside Rg1 application. Correspondingly, long‑term potentiation (LTP) was restored following ginsenoside Rg1 application in the AD mice model. Taken together, ginsenoside Rg1 repaired hippocampal LTP and memory, likely through facilitating the clearance of AD‑associated proteins and through activation of the BDNF‑TrkB pathway. Therefore, ginsenoside Rg1 may be a candidate drug for the treatment of AD. PMID:27082952
Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells
Sun, Zhi-gao; Chen, Li-ping; Wang, Fa-wei; Xu, Cheng-yong; Geng, Miao
The active ingredient of ginseng, ginsenosides Rg1, has been shown to scavenge free radicals and improve antioxidant capacity. This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2. Ginsenosides Rg1 at different concentrations (50 and 100 μM) was used to treat H2O2 (150 μM)-injured SH-SY5Y cells. Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5Y cells injured by H2O2, diminished the amount of leaked lactate dehydrogenase, and increased superoxide dismutase activity. Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity, and contributed to heat shock protein 70 gene expression, in a dose-dependent manner. These results indicate that ginsenoside Rg1 has protective effects on SH-SY5Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.
Protective effects of ginsenoside Rg1 on astrocytes and cerebral ischemic-reperfusion mice.
Sun, Chenghong; Lai, Xinqiang; Huang, Xiuyan; Zeng, Yaoying
Ginsenoside Rg1 (Rg1), one of the active ingredients in Panax ginseng, has been known to regulate many cellular processes. The purpose of this study was to investigate the protective effects of Rg1 on apoptosis in mouse cultured astrocytes in vitro and a mouse model of cerebral ischemia and reperfusion in vivo. The cell apoptosis was measured by fluorescence microplate reader and xCELLigence system and the Ca(2+) overload was recorded by confocal microscopy. The mitochondrial membrane potential and reactive oxygen species (ROS) were determined by flow cytometry. BALB/c mice were subjected to transient middle cerebral artery occlusion (MCAO) and randomly divided into four groups: Sham (sham-operated +0.9% saline), MCAO (MCAO+0.9% saline), Rg1-L (MCAO+Rg1 20 mg/kg) and Rg1-H (MCAO+Rg1 40 mg/kg). Neurological deficit scores, brain water content and infarct volume were evaluated at 24 h after reperfusion. The results showed that Rg1 significantly attenuated H2O2-induced apoptosis in astrocytes. Rg1 efficiently inhibited intracellular Ca(2+) overload, loss of mitochondrial membrane potential, and ROS production in astrocytes. In vivo study, it was also observed that Rg1 markedly reduced the neurological deficit scores, brain edema, and infarct volume in the model mice. These results suggest that Rg1 possesses significant neuroprotective effects, which might be related to the prevention of astrocytes from apoptosis. PMID:25451838
The effects of ginsenoside Rg1 on chronic stress induced depression-like behaviors, BDNF expression and the phosphorylation of PKA and CREB in rats.
Liu, Z; Qi, Y; Cheng, Z; Zhu, X; Fan, C; Yu, S Y
Depression is a common neuropsychiatric disorder which has been associated with a wide range of structural and functional changes within specific brain regions. Ginsenoside Rg1 has been shown to exert a number of neuroprotective effects as demonstrated in various in vivo and in vitro studies. However, little information is available regarding the site and mechanisms of ginsenoside Rg1 in promoting antidepressant effects. The present study aimed to investigate the neuroprotective and ameliorating effects of ginsenoside Rg1 on depression-like behavior as induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS was effective in producing depression-like behaviors in rats as indicated by decreased responses in sucrose preference and forced swim tests which were associated with ultrastructural changes in neurons within the amygdala. Moreover, levels of PKA and CREB phosphorylation and the expression of brain-derived neurotrophic factor (BDNF) were decreased in the amygdala of CUMS rats. Remarkably, chronic ginsenoside Rg1 (40mg/kg, i.p., 5weeks) treatment significantly ameliorated these behavioral and biochemical alterations associated with CUMS-induced depression. Taken together, the results of the present study demonstrate that ginsenoside Rg1 exhibits antidepressant-like effects against CUMS-induced depression. This amelioration of depression-like behaviors by ginsenoside Rg1 appears to be mediated, at least in part, by a CREB-regulated increase of BDNF expression in the amygdala of rats. Therefore, these findings reveal the therapeutic potential of ginsenoside Rg1 for use in clinical trials in the treatment of depression. PMID:26926964
Vaccine adjuvant ginsenoside Rg1 enhances immune responses against hepatitis B surface antigen in mice.
Yuan, Ding; Yuan, Qin; Cui, Qianqian; Liu, Chaoqi; Zhou, Zhiyong; Zhao, Haixia; Dun, Yaoyan; Wang, Ting; Zhang, Changcheng
The adjuvant effect of ginsenoside Rg1 on immune responses against hepatitis B surface antigen (HBsAg) in mice was investigated. Female BALB/c mice were subcutaneously injected with saline or HBsAg antigen with or without Rg1 on days 7 and 21. Samples were collected 2 weeks after the boosting for the detection of anti-HBsAg immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced in splenocytes. The innate and adaptive immune responses were measured in mice immunized as described above. The results showed that ginsenoside Rg1 had adjuvant properties in stimulating IgG, splenocyte proliferation, and mRNA expression of cytokines IFN-γ and IL-4, as well as the expression of cell surface marker TLR4 in the HBsAg-immunized mice. These results indicate that Rg1 enhances both Th1 (IgG2b and IFN-γ) and Th2 (IgG1 and IL-4) responses. In addition, the TLR4 signaling pathway is involved in the adjuvant activities of ginsenoside Rg1. PMID:27095502
Protective effects of ginsenoside Rg1 on aging Sca-1⁺ hematopoietic cells.
Zhou, Yue; Liu, Jun; Cai, Shizhong; Liu, Dianfeng; Jiang, Rong; Wang, Yaping
In adults, bone hematopoietic cells are responsible for the lifelong production of all blood cells. It is affected in aging, with progressive loss of physiological integrity leading to impaired function by cellular intrinsic and extrinsic factors. However, intervention measures, which directly inhibit the aging of hematopoietic cells, remain to be investigated. In the present study, 10 µmol/l ginsenoside Rg1 (Rg1) markedly alleviated the aging phenotypes of Sca‑1+ hematopoietic cells following in vitro exposure. In addition, the protective effects of ginsenoside Rg1 on the aging of Sca‑1+ hematopoietic cells was confirmed using a serial transplantation assay in C57BL/6 mice. The mechanistic investigations revealed that Rg1‑mediated Sca‑1+ hematopoietic cell aging alleviation was linked to a series of characteristic events, including telomere end attrition compensation, telomerase activity reconstitution and the activation of genes involved in p16‑Rb signaling pathways. Based on the above results, it was concluded that ginsenoside Rg1 is a potent agent, which acts on hematopoietic cells to protect them from aging, which has implications for therapeutic approaches in hemopoietic diseases. PMID:26045300
Ginsenoside-Rg1 induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a.
Kwok, Hoi-Hin; Chan, Lai-Sheung; Poon, Po-Ying; Yue, Patrick Ying-Kit; Wong, Ricky Ngok-Shun
Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg1 (Rg1), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg1-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg1 could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a. Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3'-UTR. Intriguingly, ginsenoside-Rg1 was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg1-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg1 could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg1, and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy. PMID:26115870
Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity.
Leung, K W; Yung, K K L; Mak, N K; Chan, Y S; Fan, T P; Wong, R N S
Ginsenoside-Rg1, the pharmacologically active component isolated from ginseng, demonstrated neuroprotective effects on primary cultured rat nigral neurons against rotenone toxicity. Rotenone, a common household pesticide known for its specific and irreversible mitochondria complex I inhibition, has been suggested to be the causal agent of Parkinson's disease (PD) by inducing degeneration of cells in the substantial nigra. The present study demonstrated that co-treatment of rotenone and Rg1 could reduce rotenone-induced cell death by 58% (SEM=+/-5.60; N=3). Rotenone-induced mitochondria membrane potential (MMP, DeltaPsim) depletion was restored and elevated by at least 38% (SEM=+/-2.15; N=3) by Rg1. In addition, Rg1 prevented cytochrome c release from the mitochrondrial membrane and increased the phosphorylation inhibition of the pro-apoptotic protein Bad through activation of the PI3K/Akt pathway. The protective effects of Rg1 was blocked by glucocorticoid receptor antagonist RU486, indicating that the action of Rg1 is mediated through glucocorticoid receptor (GR). In conclusion, Rg1 inhibits the mitochondrial apoptotic pathway and increases the survival chance of the primary cultured nigral neurons against rotenone toxicity. Thus, Rg1 and its related compounds may be developed as protective agents against neurodegenerative diseases induced by mitochondrial toxins. PMID:17123556
Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: in vitro and in vivo studies.
Yu, Lin-Chien; Chen, Sung-Ching; Chang, Wei-Chun; Huang, Ya-Chun; Lin, Kurt M; Lai, Po-Hong; Sung, Hsing-Wen
The study was designed to investigate the stability of ginsenoside Rg(1) (Rg(1)) and Re (Re), two natural herbal compounds isolated from Panax ginseng, based on their activity to promote angiogenesis in vitro and in vivo. After being treated at different temperatures, pHs, and solvent species for distinct durations, the remaining activities of Rg(1) and Re on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation were examined in vitro. Additionally, the remaining activity of each treated test agent, mixed in a growth factor-reduced Matrigel, in stimulating angiogenesis was evaluated subcutaneously in a mouse model. Basic fibroblast growth factor (bFGF) was used as a control. It was found in vitro that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF, Rg(1), or Re. However, after being treated at different temperatures, pHs, or solvent species, the remaining activity of bFGF on HUVEC behaviors reduced significantly. This observation was more significant with increasing the duration of treatment. In contrast, the activities of Rg(1) and Re remained unchanged throughout the entire course of the study. The in vivo results observed on day 7 after implantation showed that the blank control (Matrigel alone) was slightly vascularized. In contrast, the density of neo-vessels in the Matrigel plug mixed with bFGF, Rg(1), or Re was significantly enhanced. However, after being treated, the density of neo-vessels was significantly reduced in the Matrigel plug mixed with bFGF, while those of Rg(1) and Re remained unchanged. The aforementioned results suggested that Rg(1) and Re could be a novel group of nonpeptide angiogenic agents with a superior stability and may be used for the management of tissue regeneration. PMID:16962729
EFFECTS OF GINSENG AND ITS FOUR PURIFED GINSENOSIDES (Rb2, Re, Rg1, Rd) ON HUMAN PANCREATIC ISLET β CELL IN VITRO
Luo, John Z. Q.; Kim, Joseph W.; Luo, LuGuang
Ginseng has attracted interest because of its potential therapeutic role in diabetes therapy. No direct evidence has shown the effects of ginseng and its components, ginsenosides, on human islet β cell. In this study, we evaluated ginseng extract and ginsenosides (Rb2, Re, Rg1, Rd) on human pancreatic β cell function. The results provide direct evidence that ginseng extract promotes human pancreatic β cell function. Ginsenoside Rb2 increased islet β cell insulin release and promoted β cell migration. Ginsenoside Re had some impact on cell migration, but had no effect on islet function by evaluating insulin release. The other ginsenosides had no effect on insulin release and islet migration. To date, this is the first study that examines the impact of ginsenosides on human pancreatic islets in vitro. PMID:27547829
The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice
Zhao, Qun; Yang, Min; Deng, Yanping; Yu, Haitao; Wang, Linlin; Teng, Fukang; Cho, Kenka; Ma, Hongmei; Wu, Peng; Li, Xue; Wu, Wanying; Liu, Xuan; Xu, Feng; Jiang, Baohong; Guo, De-An
Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination. PMID:26690140
The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.
Zhao, Qun; Yang, Min; Deng, Yanping; Yu, Haitao; Wang, Linlin; Teng, Fukang; Cho, Kenka; Ma, Hongmei; Wu, Peng; Li, Xue; Wu, Wanying; Liu, Xuan; Xu, Feng; Jiang, Baohong; Guo, De-An
Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination. PMID:26690140
Near-infrared reflectance spectroscopy (NIRS) for rapid determination of ginsenoside Rg1 and Re in Chinese patent medicine Naosaitong pill.
Zhang, Wei; Qu, Zhengyi; Wang, Yingping; Yao, Chunlin; Bai, Xueyuan; Bian, Shuai; Zhao, Bing
Ginsenosides in plant samples have been extensively studied because protopanaxadiol saponins are ubiquitous in Chinese patent medicines, in which they can be used in promoting human health as the main active ingredients. A method for rapid determination of two ginsenosides (Rg1 and Re) in Naosaitong (NST) samples using near-infrared reflectance spectroscopy (NIRS) is studied to determine the contents of ginsenoside Rg1 and Re in this work. Partial least square (PLS) regression was used for building the calibration models, and the effects of spectral preprocessing and variable selection on the models are investigated for optimization of the models. A total of 93 samples were scanned by NIRS, and also by high performance liquid chromatography coupled to a diode array detector to determine the contents of ginsenoside Rg1 and Re. The calibration models for Rg1 and Re had high values of the coefficient of determination (R(2)) (0.9766 and 0.9764) and low root mean square error of cross validation (RMSECV) (0.0136 and 0.0104), and the values of the standard error of prediction set (SEP) are 0.00764 and 0.0103, which indicate a good correlation between reference values and NIRS predicted values. The overall results show that NIRS could be applied for the rapid determination of the contents of ginsenosides in Ginseng byproducts for pharmaceuticals that develop high-quality Chinese patent medicines. PMID:25561297
Near-infrared reflectance spectroscopy (NIRS) for rapid determination of ginsenoside Rg1 and Re in Chinese patent medicine Naosaitong pill
NASA Astrophysics Data System (ADS)
Zhang, Wei; Qu, Zhengyi; Wang, Yingping; Yao, Chunlin; Bai, Xueyuan; Bian, Shuai; Zhao, Bing
Ginsenosides in plant samples have been extensively studied because protopanaxadiol saponins are ubiquitous in Chinese patent medicines, in which they can be used in promoting human health as the main active ingredients. A method for rapid determination of two ginsenosides (Rg1 and Re) in Naosaitong (NST) samples using near-infrared reflectance spectroscopy (NIRS) is studied to determine the contents of ginsenoside Rg1 and Re in this work. Partial least square (PLS) regression was used for building the calibration models, and the effects of spectral preprocessing and variable selection on the models are investigated for optimization of the models. A total of 93 samples were scanned by NIRS, and also by high performance liquid chromatography coupled to a diode array detector to determine the contents of ginsenoside Rg1 and Re. The calibration models for Rg1 and Re had high values of the coefficient of determination (R2) (0.9766 and 0.9764) and low root mean square error of cross validation (RMSECV) (0.0136 and 0.0104), and the values of the standard error of prediction set (SEP) are 0.00764 and 0.0103, which indicate a good correlation between reference values and NIRS predicted values. The overall results show that NIRS could be applied for the rapid determination of the contents of ginsenosides in Ginseng byproducts for pharmaceuticals that develop high-quality Chinese patent medicines.
Characterization of oxygenated metabolites of ginsenoside Rg1 in plasma and urine of rat.
Wang, Jing-Rong; Tong, Tian-Tian; Yau, Lee-Fong; Chen, Cheng-Yu; Bai, Li-Ping; Ma, Jing; Hu, Ming; Liu, Liang; Jiang, Zhi-Hong
This study describes the characterization of oxygenated metabolites of ginsenoside Rg1 in rat urine and plasma. These in vivo metabolites were profiled by using UHPLC-QTOF MS-based method. On the basis of high-resolution MS/MS data, and comparison with chemically synthesized authentic compounds, nine oxygenated metabolites of Rg1 were characterized as vinaginsenosides 21 and 22 (M1 and M2), vinaginsenoside R15 (M3), 6-O-(β-d-glucopyranosyl)-20-O-(β-d-glucopyranosyl) 3β, 6α, 12β, 20(S)-tetrahydroxy-24ξ-hydroxydammar-25-ene (M4 and M5), floralginsenoside A (M7 and M8), floralginsenoside B (M9) and epoxyginsenoside Rg1 (M13), respectively. Among these metabolites, M4, M5 and M13 are new ginsenosides and others were detected as in vivo metabolites of Rg1 for the first time. In addition, a series of oxygenated metabolites of Rh1 and deglycosylated metabolite of Rg1, were observed and characterized by comparing with compounds synthesized by us, which revealed an association between C-20 configuration and the extent of oxidation metabolism. Appearance of all these metabolites in blood stream and urine after i.v. dosing and oral administration of Rg1 was further examined, which clearly showed that mono-oxygenated metabolites of Rg1 were major circulating metabolites at the early stage after dosing. Characterization of exact chemical structures of these circulating metabolites contribute greatly to our understanding of chemical exposure after consumption of ginseng products, and provide valuable information for explaining multiple bioactivities of ginseng products. PMID:26809375
Ginsenoside Rg1 reduces aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells.
Wang, Li; Mao, Nan; Tan, Rui-Zhi; Wang, Hong-Lian; Wen, Ji; Liu, Yu-Hang; Furhad, Md; Fan, Jun-Ming
Aldosterone is a steroid hormone secreted from the adrenal cortex, which regulates blood pressure. Higher concentrations of aldosterone can cause several diseases, including hypertension, diabetic nephropathy and chronic kidney disease. Previous reports have demonstrated that aldosterone has a pathogenic role in renal injury via reactive oxygen species (ROS), which involves the regulation of autophagy. However, whether aldosterone can induce autophagy in renal tubular cells remains to be elucidated. In the present study, elevated autophagy was observed in rat renal tubular NRK-52E cells exposed to aldosterone, which was demonstrated by the increased number of autophagosomes, conversion of LC3-I to LC3-II and the expression of Beclin-1. The enhanced autophagy was accompanied by increased production of intracellular ROS, which was reversed by N-acetylcysteine, a specific inhibitor of ROS signaling. Furthermore, treatment with ginsenoside Rg1 reduced the aldosterone-induced autophagy and production of ROS, possibly through reducing the phosphorylation of AMPK and preserving mTOR activity. These findings demonstrated that aldosterone promoted ROS generation and increased autophagy in the NRK-52E cells. Ginsenoside Rg1 effectively relieved aldosterone-induced oxidative stress and abnormal autophagy, suggesting that Rg1 may be used as a potential therapeutic drug to inhibit the renal injury, which is induced by aldosterone. PMID:26063203
Enzymatic transglycosylation of ginsenoside Rg1 by rice seed α-glucosidase.
Kim, Min-Ji; Kim, Young-Hoi; Song, Geun-Sup; Suzuki, Yukio; Kim, Myung-Kon
Six α-monoglucosyl derivatives of ginsenoside Rg1 (G-Rg1) were synthesized by transglycosylation reaction of rice seed α-glucosidase in the reaction mixture containing maltose as a glucosyl donor and G-Rg1 as an acceptor. Their chemical structures were identified by spectroscopic analysis, and the effects of reaction time, pH, and glycosyl donors on transglycosylation reaction were investigated. The results showed that rice seed α-glucosidase transfers α-glucosyl group from maltose to G-Rg1 by forming either α-1,3 (α-nigerosyl)-, α-1,4 (α-maltosyl)-, or α-1,6 (α-isomaltosyl)-glucosidic linkages in β-glucose moieties linked at the C6- and C20-position of protopanaxatriol (PPT)-type aglycone. The optimum pH range for the transglycosylation reaction was between 5.0 and 6.0. Rice seed α-glucosidase acted on maltose, soluble starch, and PNP α-D-glucopyranoside as glycosyl donors, but not on glucose, sucrose, or trehalose. These α-monoglucosyl derivatives of G-Rg1 were easily hydrolyzed to G-Rg1 by rat small intestinal and liver α-glucosidase in vitro. PMID:26372017
Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.
Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung
Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID:26153045
Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen
Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung
Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin−) Sca-1+ c-Kit+ haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit+ HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit+ HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit+/CD45+ HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID:26153045
Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.
Huang, Liang; Liu, Li-Feng; Liu, Juan; Dou, Ling; Wang, Ge-Ying; Liu, Xiao-Qing; Yuan, Qiong-Lan
Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aβ25-35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25-35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25-35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25-35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25-35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387
Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons
Huang, Liang; Liu, Li-feng; Liu, Juan; Dou, Ling; Wang, Ge-ying; Liu, Xiao-qing; Yuan, Qiong-lan
Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25–35 (Aβ25–35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25–35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25–35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25–35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25–35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387
Enzymatic Formation of Novel Ginsenoside Rg1-α-Glucosides by Rat Intestinal Homogenates.
Mathiyalagan, Ramya; Kim, Young-Hoi; Kim, Yeon Ju; Kim, Myung-Kon; Kim, Min-Ji; Yang, Deok Chun
The variation of linkage positions in ginsenosides leads to diverse pharmacological efficiencies. The hydrolysis and transglycosylation properties of glycosyl hydrolase family enzymes have a great impact on the synthesis of novel and structurally diversified compounds. In this study, six ginsenoside Rg1-α-glucosides were found to be synthesized from the reaction mixture of maltose as a donor and ginsenoside Rg1 as a sugar acceptor in the presence of rat small intestinal homogenates, which exhibit high α-glucosidase activities. The individual compounds were purified and were identified by spectroscopy (HPLC-MS, (1)H-NMR, and (13)C-NMR) as 6-O-[α-D-glcp-(1→4)-β-D-glcp]-20-O-(β-D-glcp)-20(S)-protopanaxatriol, 6-O-β-D-glcp-20-O-[α-D-glcp-(1→6)-(β-D-glcp)]-20(S)-protopanaxatriol, 6-O-β-D-glcp-20-O-[α-D-glcp-(1→4)-(β-D-glcp)]-20(S)-protopanaxatriol, 6-O-[α-D-glcp-(1→6)-β-D-glcp]-20-O-(β-glcp)-20(S)-protopanaxatriol, 6-O-[α-D-glcp-(1→3)-β-D-glcp]-20-O-(β-D-glcp)-20(S)-protopanaxatriol, and 6-O-β-D-glcp-20-O-[α-D-glcp-(1→3)-(β-D-glcp)]-20(S)-protopanaxatriol. Among these six, 6-O-β-D-glcp-20-O-α-D-glcp-(1→6)-(β-D-glcp)-20(S)-protopanaxatriol and 6-O-α-D-glcp-(1→6)-β-D-glcp-20-O-(β-D-glcp)-20(S)-protopanaxatriol are considered to be novel compounds of alpha-ginsenosidal saponins which pharmacological activities should be further characterized. This is the first report on the enzymatic elaboration of ginsenoside Rg1 derivatives using rat intestinal homogenates. To the best of our knowledge, it is also the first to reveal the sixth and 20th positions of an unusual α-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl sugar chain with 20(S)-protopanaxatriol saponins in Panax ginseng Mayer. PMID:26411353
Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis.
Lee, Sang-Yun; Jeong, Jin-Ju; Eun, Su-Hyeon; Kim, Dong-Hyun
Ginsenoside Rg1, one of the main constituents of Panax ginseng, exhibits anti-inflammatory effect. In a preliminary study, it was observed that ginsenoside Rg1 was metabolized to 20(S)-protopanaxtriol via ginsenosides Rh1 and F1 by gut microbiota. We further investigated the anti-inflammatory effects of ginsenoside Rg1 and its metabolites in vitro and in vivo. Ginsenosides Rg1, Rh1, and 20(S)-protopanaxtriol inhibited the activation of NF-κB activation, phosphorylation of transforming growth factor beta-activated kinase 1 and interleukin (IL)-1 receptor-associated kinase, and expression of tumor necrosis factor-α and IL-1β in lipopolysaccharide (LPS)-stimulated macrophages. They also inhibited the binding of LPS to toll-like receptor 4 on the macrophages. Orally administered ginsenoside Rg1, Rh1, or 20(S)-protopanaxtriol inhibited 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colon shortening, myeloperoxidase activity, and expression of IL-1β, IL-17, and tumor necrosis factor-α in mice with TNBS-induced colitis. They did not only inhibit TNBS-induced NF-κB activation, but also restored TNBS-induced Th17/Treg imbalance. They restored IL-10 and Foxp3 expression. Moreover, they inhibited Th17 cell differentiation in vitro. Of these metabolites, in vitro and in vivo anti-inflammatory effect of 20(S)-protopanaxtriol was the most potent, followed by Rh1. These findings suggest that ginsenoside Rg1 is metabolized to 20(S)-protopanaxtriol via ginsenosides Rh1 and F1 and these metabolites particularly 20(S)-protopanaxtriol, may ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance. PMID:26054809
Synergistic neuroprotective effect of microglial‑conditioned media treated with geniposide and ginsenoside Rg1 on hypoxia injured neurons.
Wang, Jun; Hou, Jincai; Lei, Hongtao; Fu, Jianhua; Pan, Yanshu; Liu, Jianxun
The synergistic mechanism underlying the effects of multi‑component combined drug use for complex diseases remains to be fully elucidated. Microglial activation following ischemia can either affect neural survival or cause neuronal injury. The aim of the present study was to determine the synergistic effect of geniposide and ginsenoside Rg1, based on microglial‑neuronal communication. N2a neuronal cells were divided into the following seven groups: Control group; normal cultured microglial cells in conditioned medium (N‑MG‑CM) group; oxygen‑glucose deprivation (OGD) model group; OGD‑injured MG‑CM (I‑MG‑CM) group; geniposide‑treated MG‑CM (G‑MG‑CM) group; ginsenoside Rg1‑treated MG‑CM (R‑MG‑CM) group; and combination‑treated MG‑CM (C‑MG‑CM) group. A series of assays were used to detect the effects of the different MG‑CM on neurons in terms of: (i) cell viability, determined using a Cell Counting Kit‑8; (ii) lactate dehydrogenase (LDH) leakage rate; (iii) expression of NMDAR1 and activated caspase‑3, detected using western blotting; (iv) mitochondrial transmembrane potential, determined by JC‑1; and (v) mitochondrial ultrastructural features, determined using electron microscopy. The experimental results demonstrated that MG‑CM including the integrated use of geniposide and ginsenoside Rg1 significantly protected neuronal cell viability and inhibited LDH leakage, suppressed the expression of N‑methyl‑D‑aspartate receptor subunit 1 and activated caspase‑3, increased the mitochondrial transmembrane potential and improved the mitochondrial ultrastructure. MG‑CM from separately used geniposide or ginsenoside Rg1 demonstrated differential neuroprotection at different levels. These findings revealed that the synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible approach for use. PMID:26238400
Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis
Li, Jian-ping; Gao, Yan; Chu, Shi-feng; Zhang, Zhao; Xia, Cong-yuan; Mou, Zheng; Song, Xiu-yun; He, Wen-bin; Guo, Xiao-feng; Chen, Nai-hong
Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes. PMID:24976156
An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression.
Wang, Chun-Wen; Su, Shih-Chieh; Huang, Shu-Fen; Huang, Yu-Chuan; Chan, Fang-Na; Kuo, Yu-Han; Hung, Mei-Whey; Lin, Hang-Chin; Chang, Wen-Liang; Chang, Tsu-Chung
The Na(+)/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is significantly increased in diabetic individuals and positively correlated with the pathogenesis of diabetes. The development of targeted therapeutics that can reduce the intestinal SGLT1 expression level is, therefore, important. In this study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose uptake through inhibition of SGLT1 gene expression in vivo and in vitro. Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP response element (CRE) that confers the Rg1-mediated inhibition of SGLT1 gene expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein (CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and CREB binding protein associated with an inactivated chromatin status. In addition, further studies showed that the epidermal growth factor receptor (EGFR) signaling pathway also plays an essential role in the inhibitory effect of Rg1; taken together, our study demonstrates the involvement of the EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of antihyperglycemic and antidiabetic treatments. PMID:26429938
Ginsenoside Rg1 Improves In vitro-produced Embryo Quality by Increasing Glucose Uptake in Porcine Blastocysts.
Kim, Seung-Hun; Choi, Kwang-Hwan; Lee, Dong-Kyung; Oh, Jong-Nam; Hwang, Jae Yeon; Park, Chi-Hun; Lee, Chang-Kyu
Ginsenoside Rg1 is a natural compound with various efficacies and functions. It has beneficial effects on aging, diabetes, and immunity, as well as antioxidant and proliferative functions. However, its effect on porcine embryo development remains unknown. We investigated the effect of ginsenoside Rg1 on the in vitro development of preimplantation porcine embryos after parthenogenetic activation in high-oxygen conditions. Ginsenoside treatment did not affect cleavage or blastocyst formation rates, but did increase the total cell number and reduced the rate of apoptosis. In addition, it had no effect on the expression of four apoptosis-related genes (Bcl-2 homologous antagonist/killer, B-cell lymphoma-extra large, Caspase 3, and tumor protein p53) or two metabolism-related genes (mechanistic target of rapamycin, carnitine palmitoyltransferase 1B), but increased the expression of Glucose transporter 1 (GLUT1), indicating that it may increase glucose uptake. In summary, treatment with the appropriate concentration of ginsenoside Rg1 (20 μg/mL) can increase glucose uptake, thereby improving the quality of embryos grown in high-oxygen conditions. PMID:26954154
Ginsenoside Rg1 prevents cerebral and cerebellar injury induced by obstructive jaundice in rats via inducing expression of TIPE-2.
Zhou, Tingting; Zu, Guo; Zhou, Lu; Che, Ningwei; Guo, Jing; Liang, Zhanhua
The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats. PMID:26592478
Ginsenoside Rg1 and 20(S)-Rg3 Induce IgA Production by Mouse B Cells
Park, Ha-Yan; Lee, Sang-Hoon; Lee, Kyu-Seon; Yoon, Hee-Kyung; Yoo, Yung-Choon; Lee, Junglim; Choi, Jae Eul; Kim, Pyeung-Hyeun
Ginsenosides are the major components of ginseng, which is known to modulate blood pressure, metabolism, and immune function, and has been used to treat various diseases. It has been reported that ginseng and several ginsenosides have immunoregulatory effects on the innate and T cell-mediated immune response. However, their effects on the humoral immune response have not been fully explored. The present study examined the direct effects of red ginseng extract (RGE) and ginsenosides on mouse B cell proliferation and on antibody production and the expression of germline transcripts (GLT) by mouse B cells in vitro. RGE slightly reduced B cell proliferation, but increased IgA production by LPS-stimulated B cells. Furthermore, ginsenoside Rg1 and 20(S)-Rg3 selectively induced IgA production and expression of GLTα transcripts by LPS-stimulated B cells. Collectively, these results suggest that ginsenoside Rg1 and 20(S)-Rg3 can drive the differentiation of B cells into IgA-producing cells through the selective induction of GLTα expression. PMID:26770188
Ginsenoside Rg1 and 20(S)-Rg3 Induce IgA Production by Mouse B Cells.
Park, Ha-Yan; Lee, Sang-Hoon; Lee, Kyu-Seon; Yoon, Hee-Kyung; Yoo, Yung-Choon; Lee, Junglim; Choi, Jae Eul; Kim, Pyeung-Hyeun; Park, Seok-Rae
Ginsenosides are the major components of ginseng, which is known to modulate blood pressure, metabolism, and immune function, and has been used to treat various diseases. It has been reported that ginseng and several ginsenosides have immunoregulatory effects on the innate and T cell-mediated immune response. However, their effects on the humoral immune response have not been fully explored. The present study examined the direct effects of red ginseng extract (RGE) and ginsenosides on mouse B cell proliferation and on antibody production and the expression of germline transcripts (GLT) by mouse B cells in vitro. RGE slightly reduced B cell proliferation, but increased IgA production by LPS-stimulated B cells. Furthermore, ginsenoside Rg1 and 20(S)-Rg3 selectively induced IgA production and expression of GLTα transcripts by LPS-stimulated B cells. Collectively, these results suggest that ginsenoside Rg1 and 20(S)-Rg3 can drive the differentiation of B cells into IgA-producing cells through the selective induction of GLTα expression. PMID:26770188
The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension
Background Recent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism. Methods A rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and −9 were detected by the western blot. Results Compared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9. Conclusions Our animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and
Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in a streptozotocin-induced diabetes rat model.
Yu, Haitao; Zhen, Juan; Yang, Yang; Gu, Jinning; Wu, Suisheng; Liu, Quan
Ginsenoside Rg1 has been demonstrated to have cardiovascular protective effects. However, whether the cardioprotective effects of ginsenoside Rg1 are mediated by endoplasmic reticulum (ER) stress-induced apoptosis remain unclear. In this study, among 80 male Wistar rats, 15 rats were randomly selected as controls; the remaining 65 rats received a diet rich in fat and sugar content for 4 weeks, followed by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) to establish a diabetes model. Seven days after STZ injection, 10 rats were randomly selected as diabetic model (DM) controls, 45 eligible diabetic rats were randomized to three treatment groups and administered ginsenoside Rg1 in a dosage of 10, 15 or 20 mg/kg/day, respectively. After 12 weeks of treatment, rats were killed and serum samples obtained to determine cardiac troponin (cTn)-I. Myocardial tissues were harvested for morphological analysis to detect myocardial cell apoptosis, and to analyse protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Caspase-12. Treatment with ginsenoside Rg1 (10-20 mg/kg) significantly reduced serum cTnI levels compared with DM control group (all P < 0.01). Ginsenoside Rg1 (15 and 20 mg/kg) significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Haematoxylin and eosin and Masson staining indicated that ginsenoside Rg1 could attenuate myocardial lesions and myocardial collagen volume fraction. Additionally, ginsenoside Rg1 significantly reduced GRP78, CHOP, and cleaved Caspase-12 protein expression in a dose-dependent manner. These findings suggest that ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting ER stress-induced apoptosis in diabetic rats. PMID:26869403
Evaluation of intestinal absorption of ginsenoside Rg1 incorporated in microemulison using parallel artificial membrane permeability assay.
Han, Min; Fu, Shao; Gao, Jian-Qing; Fang, Xiao-Ling
In the present study, ginsenoside Rg(1) (Rg(1)), a naturally occurring drug which is hardly absorbed in gastrointestinal (GI) tract due to its high hydrophilicity and low membrane permeability, was incorporated in different compositions of water-in-oil microemulsions (MEs). And parallel artificial membrane permeability assay (PAMPA) that have been mainly utilized for the evaluation of in vitro permeability of early drug candidates was introduced in present study, as well as rat in vivo pharmacokinetics and in vitro permeability measurements, to investigate the effect of w/o ME on Rg(1) absorption. Correlation between various models as mentioned above was further performed to estimate the feasibility of PAMPA in the application of pharmaceutical preparation studies. After being administrated intraduodenally to rats, most of MEs can enhance the intestinal absorption of Rg(1) to various extents with relative bioavailability (F(re)) ranging from 268 to 1270% using drug solution as control. This enhanced absorption of Rg(1) may be related to its increased membrane permeability induced by ME as exhibited in the PAMPA and rat in vitro permeability measurements. Meanwhile, rat in vivo pharmacokinetics-PAMPA correlation (r(2)=0.6082) is significant (p<0.05) for ME, representing a potential prospect for the application of PAMPA in the study of pharmaceutical preparation in some conditions. PMID:19483317
Ginsenoside Rg1 improves lipopolysaccharide-induced acute lung injury by inhibiting inflammatory responses and modulating infiltration of M2 macrophages.
Bao, Suhong; Zou, Yun; Wang, Bing; Li, Yinjiao; Zhu, Jiali; Luo, Yan; Li, Jinbao
Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been reported to have potent anti-inflammatory properties. However, the effect of ginsenoside Rg1 on lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice was unknown. The present study was designed to investigate the protective role of Rg1 on LPS-induced ALI and explore the potential mechanisms. The mice were divided randomly into four groups: the sham group, the LPS group and the LPS+Rg1 (40 mg/kg or 200mg/kg) pretreatment groups. All mice received Rg1 or an equivalent volume of phosphate buffer saline (PBS) intraperitoneally 1h before LPS administration. Edema quantification, histology, and apoptosis were detected 6h after LPS administration. The number of inflammatory cells, the percentage of alternative activated (M2) macrophages and the exudate quantification in bronchoalveolar lavage fluid (BALF) were evaluated. The caspase 3 expression, and the levels of phosphorylated IκB-α and p65 were tested. The results showed that the Rg1 pretreatment group markedly improved lung damage, modulated the infiltration of neutrophils and M2 macrophages, prevented the production of protein and proinflammatory cytokines in BALF, and inhibited apoptosis in lung. We also found that Rg1 suppressed NF-κB and caspase 3 activation. These data suggest that Rg1 plays a protective role against LPS-induced ALI by ameliorating inflammatory responses, regulating the infiltration of M2 macrophages, and inhibiting pulmonary cell apoptosis. PMID:26122136
Optimization of combinations of ginsenoside-Rg1, ginsenoside-Rb1, evodiamine and rutaecarpine for effective therapy of mouse migraine.
Wu, Yanchuan; Pan, Xueqiang; Xu, Yongsong; Lu, Xuran; He, Shida; He, Rui; Gong, Muxin
Wuzhuyu decoction (WZYD) is a classic traditional Chinese medicine (TCM) formula. It has been extensively used for treating migraine for thousands of years in TCM. Four potential active ingredients from WZYD, ginsenoside-Rg1 (Rg1), ginsenoside-Rb1 (Rb1), evodiamine (Ev) and rutaecarpine (Ru), were found to have positive correlations with pharmacodynamic indicators involving mouse migraine in our previous study. To find a better therapeutic effect on migraine, this research was carried out to optimize the combinations of Rg1, Rb1, Ev and Ru using the uniform design method. The results showed that Rb1 and Ev played key roles in improving the therapeutic effect on mouse migraine by strongly ameliorating pharmacodynamic indicators associated with migraine. They significantly increased the contents of 5-hydroxytryptamine, noradrenaline and dopamine in brain tissues, and reduced the content of nitric oxide in brain tissues and the activities of nitric oxide synthase in both brain tissues and blood serum. The optimal concentrations of Rb1 and Ev were 1057.4 mg/L and 312.5 mg/L, respectively. Rg1 and Ru contributed less to the overall desirability, suggesting that they had reverse effects on some pharmacodynamic indicators of this type of migraine. The verification test demonstrated by the immunohistochemical method that the optimal combination inhibited the expression of c-fos and c-jun in periaqueductal gray of mice, and strongly ameliorated pharmacodynamic indicators. These results suggested that the therapeutic effect of the optimal combination of the four ingredients was strong, and the optimal results were proven to be reliable and accurate. PMID:26711833
Ginsenoside Rg1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of p38
Zheng, Mengxiao; Zhao, Meiping; Tang, Lanlan; Zhang, Congcong; Song, Longsheng
Background Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arteriolar resistance. Pulmonary vasoconstriction has been proved to play a significant role in PAH. We previously reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). Methods In the present study, our specific objective was to investigate the role of ginsenoside Rg1, a major component of PNS, in this process and the possible underlying mechanism. The second order pulmonary rings isolated from the Sprague-Dawley rats were treated with different dosage of ginsenoside Rg1 at 8, 40, or 100 mg/L respectively, both before and during the conditions of hypoxia and hypercapnia. Contractile force changes of the rings were detected. Furthermore, SB203580, the selective inhibitor for p38 activation was applied to the rings. Pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and ginsenoside Rg1 was administered to detect the changes induced by p38. Results Under the hypoxic and hypercapnic conditions, we observed a biphasic pulmonary artery contractile response to the second pulmonary artery rings. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by ginsenoside Rg1. This effect was significantly reinforced by SB203580 (P<0.05 or P<0.01). The expression of p38 in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (P<0.05 or P<0.01) and the observed activation was attenuated by ginsenoside Rg1 (P<0.05 or P<0.01). Conclusions Our findings strongly support the significant role of ginsenoside Rg1 in the inhibition of hypoxia and hypercapnia-induced vasoconstriction by the p38 pathway. PMID:27499938
Suppression of PMA-induced tumor cell invasion and migration by ginsenoside Rg1 via the inhibition of NF-κB-dependent MMP-9 expression.
Li, Li; Wang, Yiwen; Qi, Benquan; Yuan, Dongdong; Dong, Shuying; Guo, Daohua; Zhang, Cuiling; Yu, Meiling
Ginseng has become one of the most commonly used alternative herbal medicines, and its active component, ginsenoside Rg1 has known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have yet to be investigated. In this study, we demonstrated the ability of ginsenoside Rg1 to suppress phorbol myristate acetate (PMA)-induced invasion and migration in MCF-7 breast cancer cells. MCF-7 cells were treated with ginsenoside Rg1 and incubated with or without PMA. The protein and mRNA expression of MMP-9 and MMP-2 was analyzed using Transwell and wound‑healing assays and western blotting. The results showed that suppression was associated with the reduced secretion of MMP-9, a key metastatic enzyme. MMP-9 levels were regulated transcriptionally and correlated with the suppression of NF-κB phosphorylation and DNA binding activity. Conversely, ginsenoside Rg1 did not affect MMP-2 mRNA and TIMP-1 mRNA levels, or the activation of AP-1, suggesting a specificity of pathway inhibition. Inhibition of NF‑κB activation by p65 small‑interfering RNA (siRNA) was shown to suppress PMA-induced cell invasion and migration. The siRNA studies also showed that PMA-induced MMP-9 expression is NF-κB-dependent. The results suggested that the anticancer properties of ginsenoside Rg1 may derive from its ability to inhibit invasion and migration, and that these processes are regulated in breast cancer cells through the NF-κB‑mediated regulation of MMP-9 expression. PMID:25174454
Glucocorticoid receptor is involved in the neuroprotective effect of ginsenoside Rg1 against inflammation-induced dopaminergic neuronal degeneration in substantia nigra.
Sun, Xian-Chang; Ren, Xiao-Fan; Chen, Lei; Gao, Xian-Qi; Xie, Jun-Xia; Chen, Wen-Fang
Accumulating clinical and experimental evidence suggests that chronic neuroinflammation is associated with dopaminergic neuronal death in Parkinson's disease (PD). Ginsenoside Rg1, the most active components of ginseng, possesses a variety of biological effects on the central nervous system, cardiovascular system and immune system. The present study aimed to evaluate the protective effects of ginsenoside Rg1 on lipopolysaccharide (LPS)-induced microglia activation and dopaminergic neuronal degeneration in rat substantia nigra (SN) and its potential mechanisms. Treatment with Rg1 could ameliorate the apomorphine-induced rotational behavior in LPS-lesioned rats. GR antagonist RU486 partly abolished the protective effect of Rg1. Rg1 treatment significantly attenuated LPS-induced loss of tyrosin hydroxlase (TH) positive neurons in substantial nigra par compacta (SNpc) and decreased content of dopamine (DA) and its metabolites in striatum of the lesioned side. Meanwhile, Rg1 significantly inhibited LPS-induced microglial activation and production of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide (NO). These effects were abolished by co-treatment with RU486. In addition, Rg1 treatment significantly inhibited the LPS-induced phosphorylation of IκB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) in the lesioned side of substantial nigra. These effect could be also partly blocked by RU486. Taken together, these data indicate that Rg1 has protective effects on mesencephalic dopaminergic neurons from LPS-induced microglia inflammation. GR signaling pathway might be involved in the anti-inflammatory effect of Rg1. PMID:26455404
Protective Effect of Ginsenosides Rg1 and Re on Lipopolysaccharide-Induced Sepsis by Competitive Binding to Toll-Like Receptor 4
Su, Fei; Xue, Yin; Wang, Yuemin; Zhang, Lili; Chen, Wangxue
We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1β, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. PMID:26149990
Immunomodulatory and neuroprotective effects of ginsenoside Rg1 in the MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) -induced mouse model of Parkinson's disease.
Zhou, Ting-ting; Zu, Guo; Wang, Xi; Zhang, Xiao-gang; Li, Shao; Liang, Zhan-hua; Zhao, Jie
Ginsenoside Rg1, one of the biologically active ingredients of ginseng, has been considered to be a candidate neuroprotective drug. The objective of the study was to study the protective effects of Rg1 through the peripheral and central inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Rg1 treatment protected TH-positive cells in the SNpc region from MPTP toxicity measured with immunofluoresence. The protein expression levels of TH in the SNpc region of MPTP-induced mice following treatment with Rg1 were higher than MPTP-induced mice which were tested with Western blot. The ratio of CD3(+)CD4(+) to CD3(+)CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells in the blood increased in MPTP-induced mice following treatment with Rg1 which were detected by flow cytometry analysis. Moreover, Rg1 reduced the serum concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 which were tested with enzyme-linked immunosorbent assay (ELISA). In addition, Rg1 inhibited the activation of microglia and reduced the infiltration of CD3(+) T cells into the SNpc region which were measured by immunofluorescence. Our results indicated that Rg1 may represent a promising drug for the treatment of PD via the regulation of the peripheral and central inflammation. PMID:26548343
Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4.
Su, Fei; Xue, Yin; Wang, Yuemin; Zhang, Lili; Chen, Wangxue; Hu, Songhua
We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1β, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. PMID:26149990
A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease
Li, Naijing; Liu, Ying; Li, Wei; Zhou, Ling; Li, Qing; Wang, Xueqing; He, Ping
Background Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results The impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD. PMID:26843817
Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3K/AKT/GSK-3β pathway.
Zhang, Yini; Zhang, Zhao; Wang, Haitang; Cai, Nan; Zhou, Shuang; Zhao, Yaoping; Chen, Xue; Zheng, Shaoqiang; Si, Qi; Zhang, Wei
Ginsenoside Rg1 is the primary active substance in ginseng, and it has multiple pharmacological actions. Investigations on the pharmacologic action of ginsenoside Rg1 have developed, with a particular focus on the regulation of metabolism. The present study hypothesized that the neuroprotective effects of ginsenoside Rg1 prevent cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the phosphoinositide 3‑kinase (PI3K)/AKT/glycogen synthase kinase‑3β (GSK‑3β) pathway in aged rats. Sprague‑Dawley rats were divided into isoflurane and ginsenoside Rg1 groups and were treated with 20 mg/kg ginsenoside Rg1 for 7 days. Morris water maze was performed to analyze the cognitive function of the rats. Enzyme‑linked immunosorbent assays were used to analyze the levels of malondialdehyde, glutathione, interleukin (IL)‑1β, IL‑6 and caspase 3. The protein expression levels of AKT, GSK 3β, p21WAF1/CIP1 and p53 were measured using western blot analysis. Ginsenoside Rg1 significantly improved cognitive function, and exhibited antioxidant and anti‑inflammatory effects, demonstrating the neuroprotective effects of ginsenoside Rg1 against the effect of isoflurane anesthesia in the rats. In addition, ginsenoside Rg1 significantly reduced caspase‑3 activity, upregulated the expression of PI3K/AKT/GSK‑3β and downregulated the mRNA expression levels of p21WAF1/CIP1 and p53 in the aged rats exposed to isoflurane anesthesia. The data obtained in the present study provided evidence that the neuroprotective effects of ginsenoside Rg1 prevented the cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the PI3K/AKT/GSK‑3β pathway. PMID:27485139
Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra.
Heng, Yang; Zhang, Qiu-Shuang; Mu, Zheng; Hu, Jin-Feng; Yuan, Yu-He; Chen, Nai-Hong
Parkinson's disease (PD) is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of aggregated α-synuclein in specific central nervous system (CNS) regions. Disease development is attributed to α-synuclein abnormalities, particularly aggregation and phosphorylation. The ginsenoside Rg1, an active component of ginseng, possesses neuroprotective and anti-inflammatory effects. The purpose of the present study was to evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNpc. Rg1 also alleviated the unusual MPTP-induced increase in oligomeric, phosphorylated and disease-related α-synuclein in the SNpc. In conclusion, Rg1 protects dopaminergic neurons, most likely by reducing aberrant α-synuclein-mediated neuroinflammation, and holds promise for PD therapeutics. PMID:26723869
Neuroprotective effects of ginsenoside Rg1 through the Wnt/β-catenin signaling pathway in both in vivo and in vitro models of Parkinson's disease.
Zhou, Tingting; Zu, Guo; Zhang, Xiaogang; Wang, Xi; Li, Shao; Gong, Xiaoyang; Liang, Zhanhua; Zhao, Jie
Ginsenoside Rg1 (Rg1) is a major bioactive ingredient in Panax ginseng that has low toxicity and has been shown to have neuroprotective effects. The objectives of the present study were to explore the potential of the application of Rg1 for the treatment of Parkinson's disease (PD) and to determine whether its neuroprotective effects are exerted through the Wnt/β-catenin signaling pathway by using in vivo and in vitro models of PD. In the in vivo study, Rg1 treatment ameliorated the behavioral deficits of "Pole test", and reduced dopaminergic cell loss that were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) in a dose-dependent manner in an in vivo model of PD. In the in vitro study, cell viability was increased and cell apoptosis induced by 1-methyl-4-phenylpyridinium(MPP+) was decreased by Rg1 pretreatment. Rg1 induced protective effects on the protein and mRNA expression levels of markers of the Wnt/β-catenin signaling pathway in both the in vivo and the in vitro studies, and these neuroprotective effects were blocked by DKK1 in the in vitro study. Our results provide evidence that Rg1 has neuroprotective effects in both in vivo and in vitro PD models, and these effects act through the Wnt/β-catenin signaling pathway. Taken together, these results indicate that Rg1 may exert therapeutic effects on PD via the Wnt/β-catenin signaling pathway and may therefore provide a novel approach for the treatment of PD. PMID:26525190
Synergistic Use of Geniposide and Ginsenoside Rg1 Balance Microglial TNF-α and TGF-β1 following Oxygen-Glucose Deprivation In Vitro: A Genome-Wide Survey
Wang, Jun; Hou, Jincai; Zhao, Hui; Liu, Jianxun
Ischemia-activated microglia are like a double-edged sword, characterized by both neurotoxic and neuroprotective effects. The aim of this study was to reveal the synergistic effect of geniposide and ginsenoside Rg1 based on tumor necrosis factor- (TNF-) α and transforming growth factor- (TGF-) β1 balance of microglia. BV2 microglial cells were divided into 5 groups: control, model (oxygen-glucose deprivation (OGD)), geniposide-treated, ginsenoside-Rg1-treated, and combination-treated. A series of assays were used to detect on (i) cell viability; (ii) NO content; (iii) expression (content) of TNF-α and TGF-β1; and (iv) gene expression profiles. The results showed that integrated use of geniposide and ginsenoside Rg1 significantly inhibited NO level and protected cell viability, improved the content and expression of TGF-β1, and reduced the content and expression of TNF-α. Separated use of geniposide or ginsenoside Rg1 showed different effects at different emphases. Next-generation sequencing showed that Fcγ-receptor-mediated phagocytosis pathway played a key regulatory role in the balance of TNF-α and TGF-β1 when cotreated with geniposide and ginsenoside Rg1. These findings suggest that synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible avenue for the application. PMID:26693244
Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway.
Zhan, Heqin; Huang, Feng; Ma, Wenzhuo; Zhao, Zhenghang; Zhang, Haifang; Zhang, Chong
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and high mortality rate. Panax Notoginseng Saponins (PNS), extracted from Panax Notoginseng as a traditional Asian medicine, displayed a significant anti-fibrosis effect in liver and lung. However, whether Ginsenoside Rg1 (Rg1), an important and active ingredient of PNS, exerts anti-fibrotic activity on IPF still remain unclear. In this study, we investigated the effect of Rg1 on bleomycin-induced pulmonary fibrosis in rats. Bleomycin (5 mg/kg body weight) was intratracheally administrated to male rats. Rg1 (18, 36 and 72 mg/kg) was orally administered on the next day after bleomycin. Lungs were harvested at day 7 and 28 for the further experiments. Histological analysis revealed that bleomycin successfully induced pulmonary fibrosis, and that Rg1 restored the histological alteration of bleomycin-induced pulmonary fibrosis (PF), significantly decreased lung coefficient, scores of alveolitis, scores of PF as well as contents of alpha smooth muscle actin (α-SMA) and hydroxyproline (Hyp) in a dose-dependent manner in PF rats. Moreover, Rg1 increased the expression levels of Caveolin-1 (Cav-1) mRNA and protein, lowered the expression of transforming growth factor-β1 (TGF-β1) mRNA and protein in the lung tissues of PF rats. These data suggest that Rg1 exhibits protective effect against bleomycin-induced PF in rats, which is potentially associated with the down-regulation of TGF-β1 and up-regulation of Cav-1. PMID:27476938
Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging
Li, Jing; Cai, Dachuan; Yao, Xin; Zhang, Yanyan; Chen, Linbo; Jing, Pengwei; Wang, Lu; Wang, Yaping
Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1+ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1+ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16Ink4a, Rb, p21Cip1/Waf1 and p53 in senescent Sca-1+ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1+ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16Ink4a-Rb and p53-p21Cip1/Waf1 signaling. PMID:27294914
Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.
Xue, Wei; Liu, Yang; Qi, Wen-Yuan; Gao, Yan; Li, Min; Shi, Ai-Xin; Li, Ke-Xin
The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified. PMID:27324597
Six week swimming followed by acute uptakes of ginsenoside Rg1 may affect aerobic capacity of SD rats
Haam, Saebom; Park, Hyon
[Purpose] The purpose of this study is to examine the effects of six-weeks of endurance swim training and short-term intake of Rg1 on the expression of related proteins as well as improvement of aerobic exercise capacity in 8-week-old male SD rats. [Methods] The groups were divided into placebo (NP, n=6), Rg1 (NRG, n=6), exercise+placebo (EP, n=7), and exercise+Rg1 (ERG, n=7). On completion of the 6-week swimming exercise, Rg1-intake groups were treated with acute uptakes (3 times within 24hrs) of Rg1. After the treatment, all groups were subjected to a swim to exhaustion test, and then the mass of muscle tissue, mRNA expression level and activity of citrate synthase (CS) were analyzed on plantaris. [Results] There were no differences in the effect of 6-week swimming exercise and short-term intake of Rg1 on body weight and muscle mass between groups. Although the CS mRNA expression was elevated in the exercise group and combined treatment group, there was no significant difference in CS activity. Acute uptakes of Rg1 did not affect swimming time to exhaustion, but it was increased by 235% and 314% by the 6-weeks of exercise and combined treatment of exercise and Rg1, respectively, which suggests that the combined treatment increased the effect on the capacity of aerobic exercise. [Conclusion] Based on these results, it was confirmed that even a short-term treatment of Rg1 can give an additive effect for improvement of exercise function, and additional studies are needed for the mechanisms and modes of its working. PMID:27274464
Simultaneous determination of safflor yellow A, puerarin, daidzein, ginsenosides (Rg(1), Rb(1), Rd), and notoginsenoside R(1) in rat plasma by liquid chromatography-mass spectrometry.
Yu, Zhiguo; Gao, Xiaoxia; Yuan, Hongxia; Liu, Tao; Ma, Mingyan; Chen, Xiaohui; Bi, Kaishun
A liquid chromatograph/mass spectrometry (LC/MS) method was developed for the simultaneous quantitation of seven compounds (safflor yellow A, puerarin, daidzein, ginsenosides (Rg(1), Rb(1), Rd), and notoginsenoside R(1)) in rat plasma samples with sufficient sensitivity to facilitate analysis of samples collected after an intravenous injection of Naodesheng. The plasma samples were subjected to protein precipitation with acetone, and analyzed using negative atmospheric pressure chemical ionization mass spectrometry in selected ion monitoring (SIM) mode with baicalin as an internal standard. Good linearity for all the seven compounds was observed. The intra- and inter-day precision of analysis was <15.0% for each compound, and the accuracy ranged from 90.0% to 109.0%. This quantitation method was successfully applied to a pharmacokinetic study of following intravenous injection of rats with Naodesheng. PMID:17590558
Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging.
Li, Jing; Cai, Dachuan; Yao, Xin; Zhang, Yanyan; Chen, Linbo; Jing, Pengwei; Wang, Lu; Wang, Yaping
Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1⁺ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1⁺ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16(Ink4a), Rb, p21(Cip1/Waf1) and p53 in senescent Sca-1⁺ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1⁺ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling. PMID:27294914
Ginsenoside Rg1 exerts a protective effect against Aβ₂₅₋₃₅-induced toxicity in primary cultured rat cortical neurons through the NF-κB/NO pathway.
Wu, Jiaying; Yang, Hongyu; Zhao, Qingwei; Zhang, Xingguo; Lou, Yijia
Ginsenoside Rg1 (Rg1) is a multipotent triterpene saponin extracted from ginseng, and has been proven to act as a nootropic agent against various types of neurological damage. The present study was designed to investigate the neuroprotective effect and the underlying mechanisms of Rg1 on apoptosis induced by β-amyloid peptide 25-35 (Aβ25-35) in primary cultured cortical neurons. The primary neurons were preincubated with 20 µM Rg1 for 24 h and exposed to 10 µM Aβ25-35 for 72 h. In the present study, we found that Rg1 prevented nuclear factor κ-light-chain‑enhancer of activated B cells (NF-κB) nuclear translocation and IκB-α phosphorylation in primary cultured cortical neurons after Aβ25-35 exposure by scavenging excess reactive oxygen species (ROS); ROS was measured using DCFDA and examined using a fluorescence microscope. In addition, Rg1 successfully suppressed Aβ25‑35-inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in a NF-κB-dependent manner; the suppression of NO was clearly illustrated by the NO production assay. Pretreatment of the cells with Rg1 elevated the proportion of Bcl-2/Bax, lessened the release of cytochrome c from mitochondria into cytoplasm and then blocked mitochondrial apoptotic cascades after Aβ25-35 insult by lowering NO generation. Taken together, our data demonstrate that Rg1 rescues primary cultured cortical neurons from Aβ25-35-induced cell apoptosis through the downregulation of the NF-κB/NO signaling pathway. PMID:26865401
Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.
Lee, Min Jung; Jang, Minhee; Choi, Jonghee; Chang, Byung Soo; Kim, Do Young; Kim, Sung-Hoon; Kwak, Yi-Seong; Oh, Seikwan; Lee, Jong-Hwan; Chang, Byung-Joon; Nah, Seung-Yeol; Cho, Ik-Hyun
The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE
Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.
Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan
We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. PMID:26277823
Brain distribution pharmacokinetics and integrated pharmacokinetics of Panax Notoginsenoside R1, Ginsenosides Rg1, Rb1, Re and Rd in rats after intranasal administration of Panax Notoginseng Saponins assessed by UPLC/MS/MS.
Guo, Qingli; Li, Pengyue; Wang, Zhen; Cheng, Yanke; Wu, Huichao; Yang, Bing; Du, Shouying; Lu, Yang
Panax notoginseng saponins (PNS) constitute the main active components of a traditional Chinese medicine, Panax notoginseng (Burk.) F.H. Chen (Sanqi). To investigate brain distribution of Panax Notoginsenoside R1, Ginsenosides Rg1, Rb1, Re, and Rd, and the integrated PNS in rats, their contents in cortex, striatum, hypothalamus, medulla oblongata, hippocampus and olfactory bulb were simultaneously measured by UPLC-MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal Digoxin standard. The method described here was highly efficient, with short run time, excellent specificity and sensitivity, and successfully applied for pharmacokinetics studies. NGR1, GRg1, GRb1, GRe and GRd from PNS have been detected in all six brain regions studied and quantified accurately. These findings provide more insight for further understanding of the main ways from the nasal cavity to brain as well as the migration of nasally applied drugs into the CNS parenchyma. PMID:25203723
The effects of ginsenosides to amyloid fibril formation by RCMκ-casein.
Liu, Jihua; Chen, Fanbo; Yin, Jianyuan; Bu, Fengquan; Zheng, Baohua; Yang, Miao; Wang, Yunhua; Sun, Dandan; Meng, Qin
When not incorporated into the casein micelle, isolated κ-casein spontaneously forms amyloid fibrils under physiological conditions, and is a convenient model for researching generic aspects of fibril formation. Ginsenosides have recently attracted much research interest because of the effects on aging diseases, which are always associated with amyloid fibril formation, for example, Alzheimer's, Parkinson's, and Huntington's diseases. In addition, the mechanism remains unclear that ginsenosides exert the effects against aging diseases. To address these aspects, we have investigated the ability of ginsenoside Rb1, Rc, Rg1, and Re influencing fibril formation by RCMκ-casein (reduced and carboxymethylated κ-casein), with the methods of Thioflavin T fluorescence assay, transmission electron microscopy (TEM), and intrinsic fluorescence spectroscopy. The results showed that ginsenoside Rb1 and Rg1 inhibited obviously RCMκ-CN fibrillation in both the initial rate and final level of ThT fluorescence. On the contrary, ginsenoside Re had a few effect on promoting RCMκ-CN fibril formation, proved by thick and larger fibrils observed frequently in TEM. While Rc did not influence RCMκ-CN fibrillation. It is demonstrated that Rg1 prevent RCMκ-CN fibril formation by stabilising RCMκ-CN in its native like state. Additional chemical structure difference of ginsenosides and the effects on fibril formation are also implicated. PMID:25934110
Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats.
Zhang, Zhihao; Wang, Xiaoyan; Wang, Jingcheng; Jia, Zhiying; Liu, Yumin; Xie, Xie; Wang, Chongchong; Jia, Wei
Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate the urinary metabolite profile in rats with oral administration of ginsenosides and the control group. Significant changes of urinary metabolites contents were observed in the total ginsenosides group, revealing the impact of ginsenosides as indicated by the up- or down-regulation of several pathways involving neurotransmitter-related metabolites, tricarboxylic acid (TCA) cycle, fatty acids β-oxidation, and intestinal microflora metabolites. Meanwhile, a targeted UPLC-QQQ/MS-based metabonomic approach was developed to investigate the changes of urinary ginsenoside metabolites during the process of acute cold stress. Metabolic analysis indicated that upstream ginsenosides (rg1, re, and rf) increased significantly, whereas downstream ginsenosides (ck, ppd, and ppt) decreased correspondingly after cold exposure. Finally, the relationships between ginsenosides and significantly changed metabolites were investigated by correlation analysis. PMID:27150950
Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement.
Guo, Jinhui; Chang, Li; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian
The aim of the present study was to investigate the effect of ginsenoside compound K on β-amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes. PMID:25187838
Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression.
Shang, Wenbin; Yang, Ying; Jiang, Boren; Jin, Hua; Zhou, Libin; Liu, Shangquan; Chen, Mingdao
Evidence has accumulated that ginseng and its main active constituents, ginsenosides, possess anti-diabetic and insulin-sensitizing properties which may be partly realized by regulating adipocyte development and functions. In the present study, we explored the effect of ginsenoside Rb(1), the most abundant ginsenoside in ginseng root, on adipogenesis of 3T3-L1 cells. We found that with standard differentiation inducers, ginsenoside Rb(1) facilitated adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner; 10 microM Rb(1) increased lipid accumulation by about 56%. Treatment of differentiating adipocytes with 10 microM Rb(1) increased the expression of mRNA and protein of PPARgamma(2) and C/EBPalpha, as well as mRNA of ap2, one of their target genes. After the treatment of differentiating adipocytes with Rb(1), basal and insulin-mediated glucose uptake was significantly augmented, accompanied by the up-regulation of mRNA and protein level of GLUT4, but not of GLUT1. In addition, ginsenoside Rb(1) also inhibited the proliferation of preconfluent 3T3-L1 preadipocytes. Our data indicate that anti-diabetic and insulin-sensitizing activities of ginsenosides, at least in part, are involved in the enhancing effect on PPARgamma2 and C/EBPalpha expression, hence promoting adipogenesis. PMID:17129589
RPS23RG1 reduces Aβ oligomer-induced synaptic and cognitive deficits
Yan, Li; Chen, Yaomin; Li, Wubo; Huang, Xiumei; Badie, Hedieh; Jian, Fan; Huang, Timothy; Zhao, Yingjun; Cohen, Stanley N.; Li, Limin; Zhang, Yun-wu; Luo, Huanmin; Tu, Shichun; Xu, Huaxi
Alzheimer's disease (AD) is the most common form of dementia in the elderly. It is generally believed that β-amyloidogenesis, tau-hyperphosphorylation, and synaptic loss underlie cognitive decline in AD. Rps23rg1, a functional retroposed mouse gene, has been shown to reduce Alzheimer's β-amyloid (Aβ) production and tau phosphorylation. In this study, we have identified its human homolog, and demonstrated that RPS23RG1 regulates synaptic plasticity, thus counteracting Aβ oligomer (oAβ)-induced cognitive deficits in mice. The level of RPS23RG1 mRNA is significantly lower in the brains of AD compared to non-AD patients, suggesting its potential role in the pathogenesis of the disease. Similar to its mouse counterpart, human RPS23RG1 interacts with adenylate cyclase, activating PKA/CREB, and inhibiting GSK-3. Furthermore, we show that human RPS23RG1 promotes synaptic plasticity and offsets oAβ-induced synaptic loss in a PKA-dependent manner in cultured primary neurons. Overexpression of Rps23rg1 in transgenic mice consistently prevented oAβ-induced PKA inactivation, synaptic deficits, suppression of long-term potentiation, and cognitive impairment as compared to wild type littermates. Our study demonstrates that RPS23RG1 may reduce the occurrence of key elements of AD pathology and enhance synaptic functions to counteract oAβ-induced synaptic and cognitive deficits in AD. PMID:26733416
Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor β signaling cascades.
Li, Zheng; Ryu, Seung-Wook; Lee, Jungsul; Choi, Kyungsun; Kim, Sunchang; Choi, Chulhee
Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-β-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-β-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-β signaling cascades. PMID:26820528
Variation of Ginsenosides in Ginseng of Different Ages.
He, Jian-Ming; Zhang, Yi-Zhen; Luo, Jian-Ping; Zhang, Wen-Ju; Mu, Qing
Panax ginseng has been used in traditional oriental medicine for thousands of years. Ginsenosides, the major chemical components of the roots, are considered to be responsible for the medicinal properties of ginseng. Ginsenosides increase with the age of ginseng root in general knowledge, and in this study the content of ginsenosides in ginseng of different ages was quantified. Separation and determination of eight main ginsenosides, Rg1, Re, Rb1, Rc, Rg2, Rb2, Rb3 and Rd, was performed by high performance liquid chromatography with UV detection at 203 nm. The content of Rg1, Re, Rb1, Rc, Rg2 and Rd increased from 5 to 16-year-old ginseng and then decreased, while Rb2 and Rb3 increased in the range of 5-12 years, but then slowly decreased. However, the total eight ginsenosides in 16 year old ginseng had a higher content than that in any other from 5-18 years old. As a result, the content of ginsenosides and total ginsenosides was not positively related to age from 5-18 years, which is not in full agreement with the general knowledge of ginseng. Thus, this study suggests that the older wild ginseng may not result in better medicinal ginseng for herbal medicines. PMID:27534105
The retention behavior of ginsenosides in HPLC and its application to quality assessment of Radix Ginseng.
Hu, Ping; Luo, Guo-An; Wang, Qing; Zhao, Zhong-Zhen; Wang, Wan; Jiang, Zhi-Hong
This study systematically investigated the retention behavior of seven neutral ginsenosides Rg(1), Re, Rf, Rb(1), Rb(2), Rc, Rd, and an acidic ginsenoside R(0), the major pharmacologically active components of Radix Ginseng with RP-HPLC. The effects of solvent, pH value, ionic strength of the mobile phase, and column temperature were investigated using an octadecylsiloxane-bonded silica gel column. Based on the ginsenosides' retention characteristics, the concentration of acetonitrile and the gradient of the mobile phase needed to maintain the baseline separation of the major neutral ginsenosides in Radix Ginseng were theoretically predicted. Furthermore, the ionic strength of mobile-phase necessary to achieve good resolution of the neutral ginsenosides and acidic ginsenosides was carefully investigated. According to the results of the quantitative analysis of ginsenosides in eight batches of ginseng samples from different sources, the developed HPLC technique may be a valuable tool for the quality assessment of Radix Ginseng. PMID:18958416
The retention behavior of ginsenosides in HPLC and its application to quality assessment of Radix Ginseng.
Hu, Ping; Luo, Guo-An; Wang, Qing; Zhao, Zhong-Zhen; Wang, Wan; Jiang, Zhi-Hong
This study systematically investigated the retention behavior of seven neutral ginsenosides Rg(1), Re, Rf, Rb(1), Rb(2), Rc, Rd, and an acidic ginsenoside R(0), the major pharmacologically active components of Radix Ginseng with RP-HPLC. The effects of solvent, pH value, ionic strength of the mobile phase, and column temperature were investigated using an octadecylsiloxane-bonded silica gel column. Based on the ginsenosides' retention characteristics, the concentration of acetonitrile and the gradient of the mobile phase needed to maintain the baseline separation of the major neutral ginsenosides in Radix Ginseng were theoretically predicted. Furthermore, the ionic strength of mobile-phase necessary to achieve good resolution of the neutral ginsenosides and acidic ginsenosides was carefully investigated. According to the results of the quantitative analysis of ginsenosides in eight batches of ginseng samples from different sources, the developed HPLC technique may be a valuable tool for the quality assessment of Radix Ginseng. PMID:19471880
Remarkable Impact of Acidic Ginsenosides and Organic Acids on Ginsenoside Transformation from Fresh Ginseng to Red Ginseng.
Liu, Zhi; Xia, Juan; Wang, Chong-Zhi; Zhang, Jin-Qiu; Ruan, Chang-Chun; Sun, Guang-Zhi; Yuan, Chun-Su
Panax ginseng contains many chemical components, including acidic ginsenosides and organic acids. However, whether these acidic substances play a role in ginsenoside transformation during steaming treatment has not yet been explored. In this paper, the content of neutral ginsenosides, acidic ginsenosides, and their degradation products in unsteamed and steamed P. ginseng were simultaneously quantified by high-performance liquid chromatography. We observed that neutral ginsenosides were converted to rare ginsenosides during the root steaming but not during the individual ginsenoside steaming. In contrast, acidic malonyl ginsenosides released malonic acid and acetic acid through demalonylation, decarboxylation, deacetylation reactions during the steaming at 120 °C. These malonyl ginsenosides not only were converted to rare ginsenosides but also promoted the degradation of neutral ginsenosides. Further studies indicated that a low concentration of organic acid was the determining factor for the ginsenoside conversion. The related mechanisms were deduced to be mainly acidic hydrolysis and dehydration. In summary, acidic ginsenosides and organic acids remarkably affected ginsenoside transformation during the steaming process. Our results provide useful information for precisely understanding the ginsenoside conversion pathways and mechanisms underlying the steaming process. PMID:27295137
Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells
Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury. PMID:24716802
Autotoxic Ginsenosides in the Rhizosphere Contribute to the Replant Failure of Panax notoginseng
Yang, Min; Zhang, Xiaodan; Xu, Yanguo; Mei, Xinyue; Jiang, Bingbing; Liao, Jingjing; Yin, Zhaobo; Zheng, Jianfen; Zhao, Zhi; Fan, Liming; He, Xiahong; Zhu, Youyong; Zhu, Shusheng
Background and Aims Sanqi ginseng (Panax notoginseng) growth is often hampered by replant failure. In this study, we aimed to examine the role of autotoxicity in Sanqi replant failures and assess the role of ginsenosides in autotoxicity. Methods The autotoxicities were measured using seedling emergence bioassays and root cell vigor staining. The ginsenosides in the roots, soils, and root exudates were identified with HPLC-MS. Results The seedling emergence and survival rate decreased significantly with the continuous number of planting years from one to three years. The root exudates, root extracts, and extracts from consecutively cultivated soils also showed significant autotoxicity against seedling emergence and growth. Ginsenosides, including R1, Rg1, Re, Rb1, Rb3, Rg2, and Rd, were identified in the roots and consecutively cultivated soil. The ginsenosides, Rg1, Re, Rg2, and Rd, were identified in the root exudates. Furthermore, the ginsenosides, R1, Rg1, Re, Rg2, and Rd, caused autotoxicity against seedling emergence and growth and root cell vigor at a concentration of 1.0 µg/mL. Conclusion Our results demonstrated that autotoxicity results in replant failure of Sanqi ginseng. While Sanqi ginseng consecutively cultivated, some ginsenosides can accumulate in rhizosphere soils through root exudates or root decomposition, which impedes seedling emergence and growth. PMID:25695831
Rg1 Attenuates alcoholic hepatic damage through regulating AMP-activated protein kinase and nuclear factor erythroid 2-related factor 2 signal pathways.
Gao, Yan; Chu, Shi-Feng; Xia, Cong-Yuan; Zhang, Zhao; Zhang, Shuai; Chen, Nai-Hong
Rg1 has shown multiple pharmacological activities and been considered to be evaluated for hepatic protective activity, as Rg1 could modulate different pathways in various diseases. Herein we assessed its effect and potential mechanism in a newly modified ethanol model. C57BL/6 mice were fed with Lieber-DeCarli liquid diet containing ethanol or isocaloric maltose dextrin as control diet with or without Rg1. Meanwhile, bicyclol was treated as positive drug to compare the efficacy of Rg1 against alcoholic hepatotoxicity. According to our data, Rg1 indeed improved the survival rate and lowered the abnormal high levels of serum parameters. H&E and Oil Red O staining indicated that the condition of liver damage was mitigated by Rg1 administration. Furthermore, AMPK and Nrf2 pathways were all modulated at both RNA and protein levels. In accordance with these findings, Rg1 effectively protected against alcoholic liver injury, possibly by modulating metabolism, suppressing oxidative stress, and enhancing oxidant defense systems of Nrf2 pathway. In vitro, Rg1 has no cell toxicity and promotes Nrf2 translocate into nuclear. In summary, we demonstrate that Rg1 is a potent activator of Nrf2 pathway, and could therefore be applied for prevention of hepatic damage. PMID:27229011
An FK5 analysis from RG1 Astrolabe Catalogue.
NASA Astrophysics Data System (ADS)
Perdomo, R.; Nievas, E.; Hormaechea, J. L.
RG1 Danjon Astrolabe Catalogue was elaborated from Rio Grande Station observations. It includes about 130 FK4 and FK4 Sup. stars in the B1950 system (Mondinalli et al., 1985). These coordinates can be transformed to the J2000 system. In this way, RG1 positions may be compared with those from FK5 simply transforming those from the latter to the mean epoch of RG1 (1981.5). Typical rms differences between RG1 and FK5, are 0.014 sec. in right ascension and 0.12 arc sec. in declination. However, individual differences in both coordinates up to 0.4 arc sec., presumably due to FK5 positions, are still present.
Ginsenoside-free molecules from steam-dried ginseng berry promote ethanol metabolism: an alternative choice for an alcohol hangover.
Lee, Do Ik; Kim, Seung Tae; Lee, Dong Hoon; Yu, Jung Min; Jang, Su Kil; Joo, Seong Soo
Ethanol metabolism produces harmful compounds that contribute to liver damage and cause an alcohol hangover. The intermediate metabolite acetaldehyde is responsible for alcohol hangover and CYP2E1-induced reactive oxygen species damage liver tissues. In this study, we examined whether ginsenoside-free molecules (GFMs) from steam-dried ginseng berries promote ethanol metabolism and scavenge free radicals by stimulating primary enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, and catalase) and antioxidant effects using in vitro and in vivo models. The results revealed that GFM effectively scavenged 2,2-diphenyl-1-picrylhydrazyl hydrate radicals and hydroxyl radicals. Notably, GFM significantly enhanced the expression of primary enzymes within 2 h in HepG2 cells. GFM clearly removed the consumed ethanol and significantly reduced the level of acetaldehyde as well as enhancement of primary gene expression in BALB/c mice. Moreover, GFM successfully protected HepG2 cells from ethanol attack. Of the major components identified in GFM, it was believed that linoleic acid was the most active ingredient. Based on these findings, we conclude that GFM holds promise for use as a new candidate for ethanol metabolism and as an antihangover agent. PMID:24962619
The effect of extrusion conditions on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng
Gui, Ying; Ryu, Gi Hyung
This study was conducted to investigate the effect of extrusion conditions (moisture content 20% and 30%, screw speed 200 and 250 rpm, barrel temperature 115℃ and 130℃) on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng (KRG). Extruded KRGs showed relatively higher amounts of acidic polysaccharide (6.80% to 9.34%) than nonextruded KRG (4.34%). Increased barrel temperature and screw speed significantly increased the content of acidic polysaccharide. The major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg2s, Rg3s, Rh1, and Rg3r) of KRG increased through extrusion, while the ginsenoside (Rg1) decreased. The EX8 (moisture 30%, screw speed 250 rpm, and temperature 130℃) had more total phenolics and had a better scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals than those of extruded KRG samples. The extrusion cooking showed a significant increase (6.8% to 20.9%) in reducing power. Increased barrel temperature significantly increased the values of reducing power, the highest value was 1.152 obtained from EX4 (feed moisture 20%, screw speed 250 rpm, and temperature 130℃). These results suggest that extrusion conditions can be optimized to retain the health promoting compounds in KRG products. PMID:23717175
Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation.
Cho, Young-Lai; Hur, Sung-Mo; Kim, Ji-Yoon; Kim, Ji-Hee; Lee, Dong-Keon; Choe, Jongeon; Won, Moo-Ho; Ha, Kwon-Soo; Jeoung, Dooil; Han, Sanghwa; Ryoo, Sungwoo; Lee, Hansoo; Min, Jeong-Ki; Kwon, Young-Guen; Kim, Dong-Hyun; Kim, Young-Myeong
Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE(-/-) mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca(2+)/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability. These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature. PMID:25391655
Specific Activation of Insulin-like Growth Factor-1 Receptor by Ginsenoside Rg5 Promotes Angiogenesis and Vasorelaxation*
Cho, Young-Lai; Hur, Sung-Mo; Kim, Ji-Yoon; Kim, Ji-Hee; Lee, Dong-Keon; Choe, Jongeon; Won, Moo-Ho; Ha, Kwon-Soo; Jeoung, Dooil; Han, Sanghwa; Ryoo, Sungwoo; Lee, Hansoo; Min, Jeong-Ki; Kwon, Young-Guen; Kim, Dong-Hyun; Kim, Young-Myeong
Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE−/− mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca2+/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability. These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature. PMID:25391655
Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.
Wu, Chun Fu; Bi, Xiu Li; Yang, Jing Yu; Zhan, Jia Yang; Dong, Ying Xu; Wang, Jin Hui; Wang, Ji Ming; Zhang, Ruiwen; Li, Xian
Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS-activated N9 cells. Ginsenoside-Rg1 and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-alpha and NO induction, the effect of ginsenosides on transcription factor NF-kappaB protein level was also examined. These activities were associated with the down-regulation of inhibitor kappaB (IkappaB). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation. PMID:17276889
Steamed American ginseng berry: ginsenoside analyses and anticancer activities.
Wang, Chong-Zhi; Zhang, Bin; Song, Wen-Xin; Wang, Anbao; Ni, Ming; Luo, Xiaoji; Aung, Han H; Xie, Jing-Tian; Tong, Robin; He, Tong-Chuan; Yuan, Chun-Su
This study was designed to determine the changes in saponin content in American ginseng berries after treatment by heating and to assess the anticancer effects of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120 degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3, and Rh2, increased. Rg3, a previously identified anticancer ginsenoside, increased significantly. Two hours of steaming at 120 degrees C increased the content of ginsenoside Rg3 to a greater degree than other tested ginsenosides. When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116 and 99.6% for SW-480 cells. At the same treatment concentration, the effects of unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After staining with Hoechst 33258, apoptotic cells increased significantly by treatment with steamed berry extract compared with unheated extracts. Induction of apoptosis activity was confirmed by flow cytometry after staining with annexin V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content and increases the antiproliferative effects on two human colorectal cancer cell lines. PMID:17177524
Differentiation of Isomeric Ginsenosides by Using Electron-Induced Dissociation Mass Spectrometry.
Wong, Y-L Elaine; Chen, Xiangfeng; Li, Wan; Wang, Ze; Hung, Y-L Winnie; Wu, Ri; Chan, T-W Dominic
Current phytochemical research on ginsengs focuses on the structural characterization and isomer differentiation of ginsenosides. In this Letter, electron-induced dissociation (EID) was initially investigated by analyzing isomeric ginsenosides. EID provided more structural information on their differentiation than collision-induced dissociation (CID) did. Glycosyl group migration previously observed in the CID of oligosaccharide ions could also be found in the EID of protonated Rg1. This rearrangement reaction would show substantial ambiguities in differentiating Rg1 from Rf. Although other charge carriers could alleviate this problem, the use of EID in dissociating deprotonated ginsenoside ions was superior to other techniques in terms of eliminating glycosyl group migration and generating diagnostic fragment ions for the differentiation of structural isomers. This study demonstrates a potential method to analyze natural products and thus help discover and evaluate novel compounds. PMID:27181402
Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.
Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming
Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID:26840295
Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways
Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming
Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID:26840295
Evaluation of antibacterial and anti-inflammatory activities of less polar ginsenosides produced from polar ginsenosides by heat-transformation.
Wang, Lijun; Yang, Xiushi; Yu, Xiaona; Yao, Yang; Ren, Guixing
Ginsenosides are the major active constituents in both white and red American ginseng (AG), and their pharmacological effects on central nervous, cardiovascular, and endocrine systems have been well elucidated. However, the anti-Propionibacterium acnes (P. acnes) activity of them is still unknown. In this study, 5 ginsenosides enriched fractions were obtained from the total ginsenosides extract of AG roots (TAG) by resin adsorption and heat-transformation. Resin purification decreased the total polyphenol (TP) content in the fractions. However, heat treatment increased the TP content and induced extensive conversion of the polar ginsenosides (Rg1, Re, Rb1, Rc, Rb2, Rd, and Gyp XVII) to less polar compounds (Rg2, Rg3, Rg6/F4, Rs3, and Rg5/Rk1). Only the heat-treated fraction from 65% methanol elution of the HP-20 column (HPHF) showed antibacterial activity against P. acnes (ATCC11827, MIC, 128 μg/mL; ATCC6919 MIC, 64 μg/mL), S. epidermidis (MIC, 4100 μg/mL) and S. aureus (MIC, 15000 μg/mL). In the anti-inflammatory activity assay, 10 μg/mL of HPHF significantly (P < 0.05) inhibited NO production in LPS-stimulated RAW264.7 cells. These results suggest that less polar ginsenosides enriched fraction HPHF obtained from AG might be useful to develop new types of antibacterial substances and new skin care cosmetics for acne prevention and therapy. PMID:24289140
Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb–drug interactions on OATP1B3
Jiang, Rongrong; Dong, Jiajia; Li, Xiuxue; Du, Feifei; Jia, Weiwei; Xu, Fang; Wang, Fengqing; Yang, Junling; Niu, Wei; Li, Chuan
Background and Purpose Ginsenosides are bioactive saponins derived from Panax notoginseng roots (Sanqi) and ginseng. Here, the molecular mechanisms governing differential pharmacokinetics of 20(S)-protopanaxatriol-type ginsenoside Rg1, ginsenoside Re and notoginsenoside R1 and 20(S)-protopanaxadiol-type ginsenosides Rb1, Rc and Rd were elucidated. Experimental Approach Interactions of ginsenosides with human and rat hepatobiliary transporters were characterized at the cellular and vesicular levels. A rifampin-based inhibition study in rats evaluated the in vivo role of organic anion-transporting polypeptide (Oatp)1b2. Plasma protein binding was assessed by equilibrium dialysis. Drug–drug interaction indices were calculated to estimate potential for clinically relevant ginsenoside-mediated interactions due to inhibition of human OATP1Bs. Key Results All the ginsenosides were bound to human OATP1B3 and rat Oatp1b2 but only the 20(S)-protopanaxatriol-type ginsenosides were transported. Human multidrug resistance-associated protein (MRP)2/breast cancer resistance protein (BCRP)/bile salt export pump (BSEP)/multidrug resistance protein-1 and rat Mrp2/Bcrp/Bsep also mediated the transport of the 20(S)-protopanaxatriol-type ginsenosides. Glomerular-filtration-based renal excretion of the 20(S)-protopanaxatriol-type ginsenosides was greater than that of the 20(S)-protopanaxadiol-type counterparts due to differences in plasma protein binding. Rifampin-impaired hepatobiliary excretion of the 20(S)-protopanaxatriol-type ginsenosides was effectively compensated by the renal excretion in rats. The 20(S)-protopanaxadiol-type ginsenosides were potent inhibitors of OATP1B3. Conclusion and Implications Differences in hepatobiliary and in renal excretory clearances caused markedly different systemic exposure and different elimination kinetics between the two types of ginsenosides. Caution should be exercised with the long-circulating 20(S)-protopanaxadiol-type ginsenosides as they
Neuroprotective effects of ginsenosides on neural progenitor cells against oxidative injury
Ginsenosides exhibit various neuroprotective effects against oxidative stress. However, which ginsenoside provides optimal effects for the treatment of neurological disorders as a potent antioxidant remains to be elucidated. Therefore, the present study investigated and compared the neuroprotective effects of the Rb1, Rd, Rg1 and Re ginsenosides on neural progenitor cells (NPCs) following tert-Butylhydroperoxide (t-BHP)-induced oxidative injury. Primary rat embryonic cortical NPCs were prepared from E14.5 embryos of Sprague-Dawley rats. The oxidative injury model was established with t-BHP. A lactate dehydrogenase assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were used to measure the viability of the NPCs pre-treated with ginsenosides under oxidative stress. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the activation of intracellular signaling pathways triggered by the pretreatment of ginsenosides. Among the four ginsenosides, only Rb1 attenuated t-BHP toxicity in the NPCs, and the nuclear factor (erythroizd-derived 2)-like 2/heme oxygenase-1 pathway was found to be key in the intracellular defense against oxidative stress. The present study demonstrated the anti-oxidative effects of ginsenoside Rb1 on NPCs, and suggested that Rb1 may offer potential as a potent antioxidant for the treatment of neurological disorders. PMID:26935530
Neuroprotective effects of ginsenosides on neural progenitor cells against oxidative injury.
Ye, Jun; Yao, Jian-Ping; Wang, Xu; Zheng, Minying; Li, Peng; He, Chengwei; Wan, Jian-Bo; Yao, Xiaoli; Su, Huanxing
Ginsenosides exhibit various neuroprotective effects against oxidative stress. However, which ginsenoside provides optimal effects for the treatment of neurological disorders as a potent antioxidant remains to be elucidated. Therefore, the present study investigated and compared the neuroprotective effects of the Rb1, Rd, Rg1 and Re ginsenosides on neural progenitor cells (NPCs) following tert-Butylhydroperoxide (t-BHP)-induced oxidative injury. Primary rat embryonic cortical NPCs were prepared from E14.5 embryos of Sprague-Dawley rats. The oxidative injury model was established with t‑BHP. A lactate dehydrogenase assay and terminal deoxynucleotidyl transferase dUTP nick‑end labeling staining were used to measure the viability of the NPCs pre‑treated with ginsenosides under oxidative stress. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the activation of intracellular signaling pathways triggered by the pretreatment of ginsenosides. Among the four ginsenosides, only Rb1 attenuated t‑BHP toxicity in the NPCs, and the nuclear factor (erythroizd‑derived 2)‑like 2/heme oxygenase‑1 pathway was found to be key in the intracellular defense against oxidative stress. The present study demonstrated the anti-oxidative effects of ginsenoside Rb1 on NPCs, and suggested that Rb1 may offer potential as a potent antioxidant for the treatment of neurological disorders. PMID:26935530
State-of-the-art separation of ginsenosides from Korean white and red ginseng by countercurrent chromatography.
Shehzad, Omer; Kim, Hyun Pyo; Kim, Yeong Shik
Ginseng (Panax ginseng C. A. Meyer) has been one of the most popular herbs used for nutritional and medicinal purposes by the people of eastern Asia for thousands of years. Ginsenosides, the mostly widely studied chemical components of ginseng, are quite different depending on the processing method used. A number of studies demonstrate the countercurrent chromatography (CCC) separation of ginsenosides from several sources; however, there is no single report demonstrating a one-step separation of all of these ginsenosides from different sources. In the present study, we have successfully developed an efficient CCC separation methodology in which the flow-rate gradient technique was coupled with a new solvent gradient dilution strategy for the isolation of ginsenosides from Korean white (peeled off dried P. ginseng) and red ginseng (steam-treated P. ginseng). The crude samples were initially prepared by extraction with butanol and were further purified with CCC using solvent gradients composed of methylene chloride-methanol-isopropanol-water (different ratios, v/v). Gas chromatography coupled with flame ionization detector was used to analyze the components of the two-phase solvent mixture. Each phase solvent mixture was prepared without presaturation, which saves time and reduces the solvent consumption. Finally, 13 ginsenosides have been purified from red ginseng with the new technique, including Rg1, Re, Rf, Rg2, Rb1, Rb2, Rc, Rd, Rg3, Rk1, Rg5, Rg6, and F4. Meanwhile, eight ginsenosides have been purified from white ginseng, including Rg1, Re, Rf, Rh1, Rb1, Rb2, Rc, and Rd by using a single-solvent system. Thus, the present technique could be used for the purification of ginsenosides from all types' ginseng sources. To our knowledge, this is the first report involving the separation of ginsenoside Rg2 and Rg6 and the one-step separation of thirteen ginsenosides from red ginseng by CCC. PMID:23263512
[Establishment of the model for online monitoring of the column separation and purification process by near-infrared spectroscopy and determination of total ginsenosides in Folium Ginseng].
Liu, Hua; Zhao, Xin; Qi, Tian; Qi, Yun-Peng; Fan, Guo-Rong
A method was developed for online monitoring of the constituents of ginsenoside of Folium Ginseng in the column separation and purification process using near-infrared (NIR) spectroscopy technology. Determination method of ginsenoside Rg1, Re and Rb1 was developed by high performance liquid chromatography (HPLC). After collecting 40%-ethanol eluant, their NIR spectra were detected and the contents of Rg1, Re and Rb1 were determined by the above HPLC method. The quantitative analysis models of the above three compounds and the total ginsenosides were established using partial least squares (PLS). During modeling, coefficient of determination (R2) and root mean square errors of cross-validation (RMSECV) were regarded as the indexes to select optimal wave numbers and preprocessing methods. The optimal wave numbers of ginsenoside Rg1, Re, Rb1 and total ginsenosides were all in the range of 12 000. 8 approximately 7499.8 cm-1; R2 were 0.9887, 0. 9603, 0.9905 and 0.9701, respectively; RMSECV were 0.0597, 0.0722, 0.00488 and 0.0755, respectively. A lot of samples, collected during the column separation and purification process of Folium Ginseng extract, were used to validate the predicttion effect of quantitative analysis model of total ginsenosides. As a result, the correlation coefficient of NIR predicted value and HPLC value of total ginsenosides was 0.9928 and the mean prediction recovery was 100.52%, which indicated that the prediction effect of the developed model was satisfactory. This method was proved to be fast, convenient and precise. It can be used for assaying and quality control of total ginsenosides in manufacture. PMID:24611375
Preparation and characterization of mucoadhesive enteric-coating ginsenoside-loaded microparticles.
Baek, Jong-Suep; Yeon, Won-Gi; Lee, Cho-A; Hwang, Sung-Joo; Park, Jeong-Sook; Kim, Dong-Chool; Cho, Cheong-Weon
Ginsenoside saponins are phytochemically extracted from red ginseng and have been regarded as the principal components manifesting the pharmacologic activities. Saponins are very soluble in water but poorly absorbed when orally administrated. Moreover, they have some disadvantages including the decomposition in acid medium. The aim of this study was to develop oral formulation of ginsenosides composed of enteric-coating polymer and mucoadhesive polymer considering the low stability in acid medium and the low permeability of saponins. Ginsenoside-loaded microparticles were prepared by spray dryer. The influences of various parameters such as the ratio of saponin to polymer, feed concentration, feed rate, inlet/outlet temperature and additional excipients during spray-drying were investigated. In vitro release profile of ginsenoside-loaded microparticles using additional excipients, ginsenoside saponin Rg1 or Rb1 showed an 18 or 13% release in pH 1.2 when ethyl cellulose was added. Also, ginsenoside-loaded microparticles exhibited mucoadhesive properties in the presence of chitosan. The application of these polymers is being considered as the potential strategy for improvement of bioavailability in saponin delivery, orally. PMID:24821486
Fungal sensitivity to and enzymatic deglycosylation of ginsenosides.
Zhao, Xuesong; Gao, Juan; Song, Chengcheng; Fang, Qiang; Wang, Nan; Zhao, Tianjiao; Liu, Dongbo; Zhou, Yifa
A ginseng pathogen, Cylindrocarpon destructans, and five nonpathogens were tested for their sensitivity to a total ginsenoside fraction (T-GF), a protopanaxadiol-type ginsenoside fraction (PPD-GF) and a protopanaxatriol-type ginsenoside fraction (PPT-GF) from the roots of Panax ginseng C.A. Meyer. The results showed that T-GF inhibited growth of the five ginseng nonpathogens, while it promoted growth of the ginseng pathogen C. destructans. PPT-GF and PPD-GF both inhibited the growth of the five ginseng nonpathogens, although the activity of PPT-GF was higher than that of PPD-GF. PPT-GF and PPD-GF exhibited different activities on C. destructans: PPT-GF inhibited its growth, whereas PPD-GF significantly enhanced its growth. The subsequent analysis of enzymatic degradation of ginsenosides by the test fungi showed that C. destructans can consecutively hydrolyze the terminal monosaccharide units from the sugar chains attached at C3 and C20 in PPD-type ginsenosides by extracellular glycosidase activity to yield four major products, gypenoside XVII (G-XVII), compound O, compound Mb and the ginsenoside F(2). By contrast, the ginseng nonpathogens Aspergillus nidulans and Cladosporium fulvum have no extracellular glycosidase activity toward sugar chains attached to C3 in PPD-type ginsenosides. These results indicated that ginsenosides might act as host chemical defenses, while the ginseng root pathogenic fungi might counter their toxicity by converting PPD-type ginsenosides into growth or host recognition factors. The ability of ginseng root pathogens to deglycosylate PPD-type ginsenosides may be a pathogenicity factor. PMID:22449289
Substrate specificity of β-glucosidase from Gordonia terrae for ginsenosides and its application in the production of ginsenosides Rg₃, Rg₂, and Rh₁ from ginseng root extract.
Shin, Kyung-Chul; Lee, Hye-Ji; Oh, Deok-Kun
A β-glucosidase from Gordonia terrae was cloned and expressed in Escherichia coli. The recombinant enzyme with a specific activity of 16.4 U/mg for ginsenoside Rb1 was purified using His-trap chromatography. The purified enzyme specifically hydrolyzed the glucopyranosides at the C-20 position in protopanaxadiol (PPD)-type ginsenosides and hydrolyzed the glucopyranoside at the C-6 or C-20 position in protopanaxatriol (PPT)-type ginsenosides. The reaction conditions for the high-level production of Rg3 from Rb1 by the enzyme were pH 6.5, 30°C, 20 mg/ml enzyme, and 4 mg/ml Rb1. Under these conditions, G. terrae β-glucosidase completely converted Rb1 and Re to Rg3 and Rg2, respectively, after 2.5 and 8 h, respectively. Moreover, the enzyme converted Rg1 to Rh1 at 1 h with a molar conversion yield of 82%. The enzyme at 10 mg/ml produced 1.16 mg/ml Rg3, 1.47 mg/ml Rg2, and 1.17 mg/ml Rh1 from Rb1, Re, and Rg1, respectively, in 10% (w/v) ginseng root extract at pH 6.5 and 30°C after 33 h with molar conversion yields of 100%, 100%, and 77%, respectively. The combined molar conversion yield of Rg2, Rg3, and Rh1 from total ginsenosides in 10% (w/v) ginseng root extract was 68%. These above results suggest that this enzyme is useful for the production of ginsenosides Rg3, Rg2, and Rh1. PMID:25457989
Effects of ginsenosides and their metabolites on voltage-dependent Ca(2+) channel subtypes.
Lee, Jun-Ho; Jeong, Sang Min; Kim, Jong-Hoon; Lee, Byung-Hwan; Yoon, In-Soo; Lee, Joon-Hee; Choi, Sun-Hye; Lee, Sang-Mok; Park, Yong-Sun; Lee, Jung-Ha; Kim, Sung Soo; Kim, Hyoung-Chun; Lee, Boo-Yong; Nah, Seung-Yeol
In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent Ca(2+) channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned Ca(2+) channel subtypes such as alpha(1C) (L)-, alpha(1B) (N)-, alpha(1A) (P/Q)-, a1E (R)- and a1G (T) have not been identified. Here, we used the two-microelectrode volt-age clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on Ba(2+) currents (IBa) in Xenopus oocytes expressing five different Ca(2+) channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the a1G-type. Of the various ginsenosides, Rb(1), Rc, Re, Rf, Rg(1), Rg(3), and Rh(2), ginsenoside Rg(3) also inhibited all five channel subtypes and ginsenoside Rh(2) had most effect on the a1C- and a1E-type Ca(2+) channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the a(1G)-type of Ca(2+) channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. Rg(3), Rh(2), and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the alpha(1B)- and alpha(1A)-types. These results reveal that Rg(3), Rh(2) and CK are the major inhibitors of Ca(2+) channels in Panax ginseng, and that they show some Ca(2+) channel selectivity. PMID:16511347
Characterization of Panax ginseng UDP-Glycosyltransferases Catalyzing Protopanaxatriol and Biosyntheses of Bioactive Ginsenosides F1 and Rh1 in Metabolically Engineered Yeasts.
Wei, Wei; Wang, Pingping; Wei, Yongjun; Liu, Qunfang; Yang, Chengshuai; Zhao, Guoping; Yue, Jianmin; Yan, Xing; Zhou, Zhihua
Ginsenosides, the main pharmacologically active natural compounds in ginseng (Panax ginseng), are mostly the glycosylated products of protopanaxadiol (PPD) and protopanaxatriol (PPT). No uridine diphosphate glycosyltransferase (UGT), which catalyzes PPT to produce PPT-type ginsenosides, has yet been reported. Here, we show that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosylates the C20-OH of PPT to produce bioactive ginsenoside F1. We report the characterization of four novel UGT genes isolated from P. ginseng, sharing high deduced amino acid identity (>84%) with UGTPg1. We demonstrate that UGTPg100 specifically glycosylates the C6-OH of PPT to produce bioactive ginsenoside Rh1, and UGTPg101 catalyzes PPT to produce F1, followed by the generation of ginsenoside Rg1 from F1. However, UGTPg102 and UGTPg103 were found to have no detectable activity on PPT. Through structural modeling and site-directed mutagenesis, we identified several key amino acids of these UGTs that may play important roles in determining their activities and substrate regio-specificities. Moreover, we constructed yeast recombinants to biosynthesize F1 and Rh1 by introducing the genetically engineered PPT-producing pathway and UGTPg1 or UGTPg100. Our study reveals the possible biosynthetic pathways of PPT-type ginsenosides in Panax plants, and provides a sound manufacturing approach for bioactive PPT-type ginsenosides in yeast via synthetic biology strategies. PMID:26032089
Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.
Chen, Feng; Eckman, Elizabeth A; Eckman, Christopher B
For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease. PMID:16636099
Ginsenosides Rb₁ and Rd regulate proliferation of mature keratinocytes through induction of p63 expression in hair follicles.
Li, Zheng; Li, Jing-Jie; Gu, Li-Juan; Zhang, Dong-Liang; Wang, Yun-Bo; Sung, Chang-Keun
Ginsenosides Rb₁ and Rd are the two main types of ginsenosides in Panax ginseng and have been used as an additive to against alopecia. However, the mechanisms involved are largely unknown. To determine how ginsenosides prevent hair loss, we topically applied protopanaxadiol-type ginsenosides Rb₁ and Rd over the shaved skin of B57CL/6 mice, and monitored and assessed them for 35 days. We then investigated the effects of ginsenosides on cell genesis in different phases of adult hair follicles (HFs), using 5-bromo-2'-deoxyuridine as a marker for dividing cells. Moreover, p63, a specific marker and a major regulator of keratinocyte progenitor cells of the multi-layered epithelia, was detected in epidermis. Results indicated that treatment with ginsenosides Rb₁ and Rd increased cell proliferation in both anagen and telogen of HFs. However, it had no significant effect on the survival of cells in the bulge and upper follicle region. Investigation of p63 demonstrated that up-regulation of p63 expression in the matrix and outer root sheath might be one of the mechanisms by which ginsenosides Rb₁ and Rd promote cell proliferation in HFs. Our study reveals a novel mechanism by which ginsenoside promotes hair growth through p63 induction in follicular keratinocytes and indicates that ginsenosides Rb₁ and Rd might be developed as a therapeutic agent for the prevention of hair loss. PMID:23007914
Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.
Ardah, Mustafa T; Paleologou, Katerina E; Lv, Guohua; Menon, Sindhu A; Abul Khair, Salema B; Lu, Jia-Hong; Safieh-Garabedian, Bared; Al-Hayani, Abdulmonem A; Eliezer, David; Li, Min; El-Agnaf, Omar M A
Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders. PMID:25449909
Simultaneous determination of notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re and 20(S) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation.
Wu, Huichao; Liu, Huimin; Bai, Jie; Lu, Yang; Du, Shouying
20(S) protopanaxatriol is the main metabolite of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re in Panax notoginseng and has significant activities. A ultra high performance liquid mass spectrometry method has been developed and validated for the simultaneous determination of notoginsenoside R₁ (R1), ginsenoside Rg₁ (Rg₁), ginsenoside Re (Re) and 20(S) protopanaxatriol (PPT) in beagle dog plasma after oral administration of a Panax notoginseng saponin preparation. After the addition of the internal standard (digoxin), plasma samples were subjected to liquid-liquid extraction with acetone and methanol and separated on a 100 × 2.1 mm ACQUITY 1.7 μm C₁₈ column (Waters, USA), with acetonitrile and water as the mobile phase, within a runtime of 7.0 min. The analytes were detected without interference in Selected Reaction Monitoring mode with a change in the electrospray ionization from positive to negative. The detection limits were 0.01 to 0.04 mg/L and the calibration curves of the peak areas for the four ingredients were linear over four orders of magnitude with a correlation coefficient greater than 0.9957. The intra-day and inter-day precision values (relative standard deviation, RSD, %) were within 10.25% and 13.51%, respectively, and the accuracy (relative error, RE, %) was less than 7.81%. The validated method was successfully applied to a comparative pharmacokinetic study of four saponins in beagle dogs after oral administration of a Panax Notoginseng Saponins preparation. The pharmacokinetic parameters were calculated with DAS 3.20. The Tmax and Cmax values indicate a dose-dose relationship between the saponins (R1, Rg1, and Re) and their sapogenin (PPT). PMID:25463196
Simultaneous quantification of 19 ginsenosides in black ginseng developed from Panax ginseng by HPLC-ELSD.
Sun, Bai-Shen; Gu, Li-Juan; Fang, Zhe-Ming; Wang, Chun-yan; Wang, Zhen; Lee, Mi-Ra; Li, Zheng; Li, Jing-Jie; Sung, Chang-Keun
A high-performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD) has been developed to identify and quantify 19 ginsenosides (Rg(1), Re, Rf, Rb(1), Rc, Rb(2), Rd, F(4), Rg(6), Rk(3), Rh(4), 20(S)-, 20(R)-Rg(3), 20(S)-, 20(R)-Rs(3), Rk(1), Rg(5), Rs(4), and Rs(5)) in black ginseng (BG, Korean white ginseng that was subjected to nine cycles of steam treatment). Ultrasonication is employed for sample preparation, and the analysis is achieved on a Discovery C(18) column using gradient elution of CH(3)CN-H(2)O-CH(3)COOH without buffer in 40min. The method was validated by linearity (r(2)> or =0.9994), precision (92.0-107.5%), intra- and inter-day accuracy (R.S.D.<3.21%), and limit of detection (LOD< or =93ng). The quantification method was applied to analyze the composition of ginsenosides in Korean white, red, and black ginsengs. During the preparatory process of BG, ginsenosides transform into constituents of low polarity by hydrolysis, isomerization, and dehydration at C-20, and hydrolysis also occurs at C-3 or C-6. The validated HPLC method is expected to provide the basis for the quality assessment of ginseng products. PMID:19394786
Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.
Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog
To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB. PMID:27582326
Comparative Pharmacokinetics of Ginsenoside Rg3 and Ginsenoside Rh2 after Oral Administration of Ginsenoside Rg3 in Normal and Walker 256 Tumor-bearing Rats
Fan, He; Xiao-ling, Sun; Yaliu, Su; Ming-ming, Lu; Xue, Feng; Xian-sheng, Meng; Li, Fu
Background: Ginseng is Chinese traditional herbal medicine, and the ginsenoside Rg3 is the main bioactive ingredient for the anti-tumor effect. However, there is no study on pharmacokinetics (PKs) of ginsenoside Rg3 and its main metabolite after oral ginsenoside Rg3 in tumor-bearing plasma. The aim of this study was to investigate the PK profiles of ginsenoside Rg3 and ginsenoside Rh2 after oral administration of pure ginsenoside Rg3 were administered, and compare the difference of the PK profiles between normal and Walker 256 tumor-bearing rats. Materials and Methods: The concentrations of two ginsenosides in plasma were determined by using a simple and rapid high-performance liquid chromatography. All the rats were divided randomly into two groups (Walker 256 tumor-bearing and normal groups). Each group received oral administration of 50 mg/kg ginsenoside Rg3. Results: The results showed that ginsenoside Rh2, possibly as a glycosylation hydrolysis product of ginsenoside Rg3, were found in plasma after oral administration of ginsenoside Rg3 to rats. Ginsenoside Rg3 had shown better absorption than ginsenoside Rh2, whether the oral administration of ginsenoside Rg3, normal rats showed better absorption than tumor-bearing rats. Discussion and Conclusion: The PKs properties of the ginsenoside Rg3 and ginsenoside Rh2 differed between tumor-bearing rats and normal rats, including area under the plasma level/time curve and concentration maximum (P < 0.05). SUMMARY Ginsenoside Rh2 was found in plasma after oral administration of ginsenoside Rg3 to ratsHPLC could be used to determine simultaneously, the concentration of ginsenoside Rg3 and ginsenoside Rh2 in rat plasma after oral administration of ginsenoside Rg3Normal rats showed better absorption than tumor-bearing rats after oral administration of ginsenoside Rg3.0. PMID:27019557
COL Application Content Guide for HTGRs: Revision to RG 1.206, Part 1 - Status Report
Wayne Moe
A combined license (COL) application is required by the Nuclear Regulatory Commission (NRC) for all proposed nuclear plants. The information requirements for a COL application are set forth in 10 CFR 52.79, "Contents of Applications; Technical Information in Final Safety Analysis Report." An applicant for a modular high temperature gas-cooled reactor (HTGR) must develop and submit for NRC review and approval a COL application which conforms to these requirements. The technical information necessary to allow NRC staff to evaluate a COL application and resolve all safety issues related to a proposed nuclear plant is detailed and comprehensive. To this, Regulatory Guide (RG) 1.206, "Combined License Applications for Nuclear Power Plants" (LWR Edition), was developed to assist light water reactor (LWR) applicants in incorporating and effectively formatting required information for COL application review (Ref. 1). However, the guidance prescribed in RG 1.206 presumes a LWR design proposal consistent with the systems and functions associated with large LWR power plants currently operating under NRC license.
Improved Inflammatory Balance of Human Skeletal Muscle during Exercise after Supplementations of the Ginseng-Based Steroid Rg1
Hou, Chien-Wen; Lee, Shin-Da; Kao, Chung-Lan; Cheng, I-Shiung; Lin, Yu-Nan; Chuang, Sheng-Ju; Chen, Chung-Yu; Ivy, John L.; Huang, Chih-Yang; Kuo, Chia-Hua
The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1 suppressed the exercise-induced increases in thiobarbituric acids reactive substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max) was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max increased significantly by ~20% (P<0.05). Conclusion: Our result suggests that Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory shift under exercise challenge. PMID:25617625
Interaction of the ginsenosides with κ-casein and their effects on amyloid fibril formation by the protein: Multi-spectroscopic approaches.
Chen, Fanbo; Wang, Yunhua; Yang, Miao; Yin, Jianyuan; Meng, Qin; Bu, Fengquan; Sun, Dandan; Liu, Jihua
The interaction of the ginsenosides (GS) including ginsenoside Rg1, Rb1 and Re with κ-casein and the effects of GS inhibiting amyloid fibril formation by κ-casein have been investigated in vitro by fluorescence and ultraviolet spectra. Results showed that Rg1 and Rb1 had dose-dependent inhibitory effects on reduced and carboxymethylated κ-casein (RCMκ-CN) fibril formation, while Re resulted in an increase in the rate of fibril formation. The enhancement in RLS intensity was attributed to the formation of new complex between GS and RCMκ-CN, and the corresponding thermodynamic parameters (ΔH, ΔS and ΔG) were assayed. The steady-state ultraviolet-visible absorption spectra had also been tested to observe if the ground-state complex formed, and it showed the same result as RLS spectra. The binding constants and the number of binding sites between GS and RCMκ-CN at different temperatures had been evaluated from relevant fluorescence data. According to the Förster non-radiation energy transfer theory, the binding distance between RCMκ-CN and GS was calculated. The fluorescence lifetime of RCMκ-CN was longer in the presence of GS than in absence of GS, which was evident that the hydrophobic interaction plays a major role in the binding of GS to RCMκ-CN. From the results of synchronous fluorescence, it could be deduced that the polarity around RCMκ-CN Trp97 residue decreased and the hydrophobicity increased after addition of Rg1 or Rb1. Based on all the above results, it is explained that Rg1 and Rb1 inhibited amyloid fibril formation by κ-casein because the molecular spatial conformation and physical property of κ-casein changed causing by the complex formation between GS and κ-casein. PMID:27163725
[Determination of Ginsenosides Amount and Geographical Origins of Ginseng by NIR Spectroscopy].
Wang, Jing-jing; Yan, Shu-mo; Yang, Bin
In the study, 74 samples of ginseng were harvested from three provinces located in the northeast of China. Method for the quantification of total amount of ginsenosides Rg1, Rb1, and Re in samples with near infrared (NIR) spectroscopy was developed with the application of partial least squares regression (PLSR). The reference analysis was performed using a UPLC method. Different pretreatments like multiplicative scatter correction (MSC), Norris-Derivative were applied on the spectra to optimize the calibration and the spectral regions from 6001 to 4007 cm(-1) and from 10,000 to 8786 cm(-1) were selected for the calculation of the PLSR model. The root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP) were 0.115 and 0.167, respectively, and the correlation coefficients were 0.9477 and 0.9153, respectively. At the same time, the spectral region from 8531 to 7559 cm(-1) was chosen to establish a model for identification the geographical origins of ginseng samples. MSC and Savitzky-Golay smoothing were utilized on the spectral preprocessing. According to the result, 74 samples were separated into three clusters, corresponding to the three geographical origins, i.e., Jilin, Liaoning and Heilongjiang Province. The cross-validation ability and the prediction ability were 96% and 90%, respectively. In Chinese Pharmacopeia, the total amount of ginsenosides Rg1, Rb1, and Re is used as one of the indexes to evaluate the quality of ginseng, the established quantification method herein is rapid and accurate, it can be applied as an alternative method for quality control of ginseng sample. PMID:26717745
Development of a secondary antibody thio-functionalized microcantilever immunosensor and an ELISA for measuring ginsenoside Re content in the herb ginseng.
Nan, Tiegui; Wu, Shangquan; Zhao, Hongwei; Tan, Weiming; Li, Zhaohu; Zhang, Qingchuan; Wang, Baomin
Ginsenoside Re (GRe) is a major active component of the Chinese medicinal herb ginseng, Panax ginseng . A sensitive and specific monoclonal antibody (mAb), designated as mAb3D6, was generated with a GRe-bovine serum albumin conjugate as an immunogen. Microcantilever immunosensors (MCS), one modified with thiolated anti-GRe antibody and one modified with thiolated goat antimouse immunoglobulin G (IgG), were developed to detect the content of ginsenoside. The MCS immobilized with thiolated goat antimouse IgG had a better sensitivity than the MCS modified with thiolated anti-GRe antibody. The advantage of a secondary antibody thio-functionalized MCS was verified with the anti-paclitaxel mAb. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was also established with mAb3D6. The concentration of analyte producing 50% inhibition and the working range of icELISA were 1.20 and 0.15-16.1 ng/mL, respectively. The icELISA had a cross-reactivity of 89% with ginsenoside Rg1 and less than 3% with other ginsenosides. The icELISA and MCS with thiolated secondary antibody were applied for the determination of GRe in ginseng samples, and the results agreed well with those determined by high-performance liquid chromatography. PMID:22494059
Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control.
Kim, Su Na; Ha, Young Wan; Shin, Heungsop; Son, Sung Ho; Wu, Song Ji; Kim, Yeong Shik
A new method of high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) was developed for the simultaneous quantification of 14 major ginsenosides, which are the marker compounds of Panax ginseng C.A. Meyer (Korean red ginseng). Various types of ginseng samples were extracted, and the amounts of the 14 ginsenosides (Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2, Rb3, Rd, Rg3, Rk1, Rg5, and Rh2) were determined by reverse-phase HPLC-ELSD using digoxin as an internal standard. The mobile phase consisted of a programmed gradient of aqueous acetonitrile. Calibration curves for each ginsenoside were determined for the quantification. The method was validated for linearity, precision, accuracy, limit of detection, and limit of quantification. This quantification method was applied to several finished ginseng products including white ginseng, red ginseng powder, and red ginseng concentrate. The amounts of the 14 ginsenosides in the various ginseng samples could be analyzed simultaneously. This validated HPLC method is expected to provide a new basis for the quality assessment of ginseng products. PMID:17560064
Pharmacokinetic Compatibility of Ginsenosides and Schisandra Lignans in Shengmai-san: From the Perspective of P-Glycoprotein
Liang, Yan; Zhou, Yuanyuan; Zhang, Jingwei; Rao, Tai; Zhou, Lijun; Xing, Rong; Wang, Qian; Fu, Hanxu; Hao, Kun; Xie, Lin; Wang, Guangji
Background Phytochemical-mediated alterations in P-glycoprotein (P-gp) activity may result in herb-drug interactions by altering drug pharmacokinetics. Shengmai-san, a traditional Chinese herbal medicine composed by Panax Ginseng, Ophiopogon Japonicus, and Schisandra Chinensis, is routinely being used for treating various coronary heart diseases. In our previous studies, Schisandra Lignans Extract (SLE) was proved as a strong P-gp inhibitor, and herein, the compatibility of Shengmai-san was studied by investigating the influence of SLE on the pharmacokinetics of the ginsenosides from the perspective of P-gp. Methodology Pharmacokinetic experiments were firstly performed based on in vitro uptake, efflux and transport experiments in Caco-2, LLC-PK1 wild-type and MDR1-overexpressing L-MDR1 cells. During the whole experiment, digoxin, a classical P-gp substrate, was used as a positive control drug to verify the cells used are the valid models. Meanwhile, the effects of SLE on the pharmacokinetics of ginsenosides were further investigated in rats after single-dose and multi-dose of SLE. Results and Conclusions The efflux ratios of ginsenoside Rb2, Rc, Rg2, Rg3, Rd and Rb1 were found more than 3.5 in L-MDR1 cells and can be decreased significantly by verapamil (a classical P-gp inhibitor). Contrarily, the efflux ratios of other ginsenosides (Rh1, F1, Re, and Rg1) were lower than 2.0 and not affected by verapamil. Then, the effects of SLE on the uptake and transport of ginsenosides were investigated, and SLE was found can significantly enhance the uptake and inhibit the efflux ratio of ginsenoside Rb2, Rc, Rg2, Rg3, Rd and Rb1 in Caco-2 and L-MDR1 cells. Besides, In vivo experiments showed that single-dose and multi-dose of SLE at 500 mg/kg could increase the area under the plasma concentration time curve of Rb2, Rc and Rd significantly without affecting terminal elimination half-time. In conclusion, SLE could enhance the exposure of ginsenosides Rb2, Rc, Rg2, Rg3, Rd and
[Research of chemotaxis response of Botrytis cinerea and Alternaria panax on total ginsenosides].
Chi, Kun; Xu, Yong-hua; Lei, Feng-jie; Yin, Min-jing; Wang, Zhuang; Zhang, Ai-hua; Zhang, Lian-xue
In this paper, three kinds of chemotactic parameters (concentration, temperature and pH) were determined by plate assay and spore germination method to research the chemotactic response of Botrytis cinerea and Alternaria panax, and their spores on total ginsenosides. The results showed that Botrytis cinerea had strong chemotactic response at the mid-concentration of total ginsenosides (cultivation temperature was 20 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.293 0, chemotactic growth rate (CGR) was 0.476 0, spore germination rate (SGR) was 53%, and dry weight of mycelial (DWM) was 0.452 6 g x L(-1); however, Alternaria panax had strong chemotactic response at the low-concentration of total ginsenosides (cultivation temperature was 25 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.235 4, chemotactic growth rate (CGR) was 0.537 0, spore germination rate (SGR) was 67%, and dry weight of mycelial (DWM) was 0.494 8 g x L(-1). The results indicated that the low and middle concentration (2, 20 mg x L(-1)) of total ginsenosides had significant promoting effect on chemotactic response of these two pathogens, and the spore germination, mycelial growth rate, dry weight of mycelial of them were also significantly improved by this chemotactic response, whereas it decreased as the increase of total ginsenosides concentration. PMID:26975095
Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson's disease.
Zhang, Xinmu; Wang, Yingzi; Ma, Cheng; Yan, Yan; Yang, Yang; Wang, Xin; Rausch, Wolf-Dieter
Ginsenosides are the main active constituents of Panax ginseng. Ginsenoside Re is one of the major ginsenosides; whereas hydrolysis products such as Rd appear to have higher biological activity though are present in smaller amounts. Ginsenosides, from their early use in folk medicine to modern studies, appear to exert beneficial actions against aging and even neurodegenerative disorders. Parkinson's disease is a progressive neurodegenerative movement disorder characterized by a profound loss of midbrain dopamine neurons in the substantia nigra pars compacta. Carbon tetrachloride (CCl4) exerts neurotoxic effects when present as an environmental pollutant. As a model compound it was used here to study the impact on primary nigrostriatal dopaminergic nerve cells and to investigate the neuroprotective potential of ginsenosides Rd and Re against this organic solvent. CCl4 (2.5 mM on day 12 in vitro for 48 h) significantly decreased the number of tyrosine hydroxylase (TH+) cells by 51% compared with untreated control cultures, reduced their neuritic lengths, and led to truncated degenerations of cell morphology. Ginsenosides Rd and Re (10 µM) strongly reduced cell loss and degeneration and significantly protected process lengths and numbers of neurites of TH+ cells. The anti-oxidative and anti-inflammatory potential of the cellular supernatant was lowered by CCl4 exposure. Inclusion of ginsenosides inhibited both oxidative stress and inflammation. Therefore the neuroprotective effects of ginsenosides at least partially depend on lowering oxidative stress and anti-inflammation. PMID:27073742
Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson's disease
Zhang, Xinmu; Wang, Yingzi; Ma, Cheng; Yan, Yan; Yang, Yang; Wang, Xin; Rausch, Wolf-Dieter
Ginsenosides are the main active constituents of Panax ginseng. Ginsenoside Re is one of the major ginsenosides; whereas hydrolysis products such as Rd appear to have higher biological activity though are present in smaller amounts. Ginsenosides, from their early use in folk medicine to modern studies, appear to exert beneficial actions against aging and even neurodegenerative disorders. Parkinson's disease is a progressive neurodegenerative movement disorder characterized by a profound loss of midbrain dopamine neurons in the substantia nigra pars compacta. Carbon tetrachloride (CCl4) exerts neurotoxic effects when present as an environmental pollutant. As a model compound it was used here to study the impact on primary nigrostriatal dopaminergic nerve cells and to investigate the neuroprotective potential of ginsenosides Rd and Re against this organic solvent. CCl4 (2.5 mM on day 12 in vitro for 48 h) significantly decreased the number of tyrosine hydroxylase (TH+) cells by 51% compared with untreated control cultures, reduced their neuritic lengths, and led to truncated degenerations of cell morphology. Ginsenosides Rd and Re (10 µM) strongly reduced cell loss and degeneration and significantly protected process lengths and numbers of neurites of TH+ cells. The anti-oxidative and anti-inflammatory potential of the cellular supernatant was lowered by CCl4 exposure. Inclusion of ginsenosides inhibited both oxidative stress and inflammation. Therefore the neuroprotective effects of ginsenosides at least partially depend on lowering oxidative stress and anti-inflammation. PMID:27073742
Biosynthesis and biotechnological production of ginsenosides.
Kim, Yu-Jin; Zhang, Dabing; Yang, Deok-Chun
Medicinal plants are essential for improving human health, and around 75% of the population in developing countries relies mainly on herb-based medicines for health care. As the king of herb plants, ginseng has been used for nearly 5,000 years in the oriental and recently in western medicines. Among the compounds studied in ginseng plants, ginsenosides have been shown to have multiple medical effects such as anti-oxidative, anti-aging, anti-cancer, adaptogenic and other health-improving activities. Ginsenosides belong to a group of triterpene saponins (also called ginseng saponins) that are found almost exclusively in Panax species and accumulated especially in the plant roots. In this review, we update the conserved and diversified pathway/enzyme biosynthesizing ginsenosides which have been presented. Particularly, we highlight recent milestone works on functional characterization of key genes dedicated to the production of ginsenosides, and their application in engineering plants and yeast cells for large-scale production of ginsenosides. PMID:25747290
Producing aglycons of ginsenosides in bakers' yeast
Dai, Zhubo; Wang, Beibei; Liu, Yi; Shi, Mingyu; Wang, Dong; Zhang, Xianan; Liu, Tao; Huang, Luqi; Zhang, Xueli
Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal plant that exhibits diverse pharmacological activities. Protopanaxadiol, protopanaxatriol and oleanolic acid are three basic aglycons of ginsenosides. Producing aglycons of ginsenosides in Saccharomyces cerevisiae was realized in this work and provides an alternative route compared to traditional extraction methods. Synthetic pathways of these three aglycons were constructed in S. cerevisiae by introducing β-amyrin synthase, oleanolic acid synthase, dammarenediol-II synthase, protopanaxadiol synthase, protopanaxatriol synthase and NADPH-cytochrome P450 reductase from different plants. In addition, a truncated 3-hydroxy-3-methylglutaryl-CoA reductase, squalene synthase and 2,3-oxidosqualene synthase genes were overexpressed to increase the precursor supply for improving aglycon production. Strain GY-1 was obtained, which produced 17.2 mg/L protopanaxadiol, 15.9 mg/L protopanaxatriol and 21.4 mg/L oleanolic acid. The yeast strains engineered in this work can serve as the basis for creating an alternative way for producing ginsenosides in place of extractions from plant sources. PMID:24424342
A Boronic Acid Porphyrin Receptor for Ginsenoside Sensing
Hargrove, Amanda E.; Reyes, Ryan N.; Riddington, Ian; Anslyn, Eric V.; Sessler, Jonathan L.
Ginsenoside detection was pursued through the design of a porphyrin receptor containing two boronic acid units. This receptor was found to undergo different degrees of fluorescence quenching with five ginsenoside guests and an acylated derivative. The trends in the 1:1 binding constants, as well as ESI-HRMS analysis, support a binding mode in which the ginsenoside sugar units are bound to the boronic acid groups while the steroid core and porphyrin ring participate in hydrophobic interactions. PMID:20860384
Identification and Characterization of a Mucilaginibacter sp. Strain QM49 β-Glucosidase and Its Use in the Production of the Pharmaceutically Active Minor Ginsenosides (S)-Rh1 and (S)-Rg2
Cui, Chang-Hao; Liu, Qing-Mei; Kim, Jin-Kwang; Sung, Bong-Hyun; Kim, Song-Gun
Here, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) from Mucilaginibacter sp. strain QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity, bglQM, consists of 2,346 bp and is predicted to encode 781 amino acid residues. This enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed in Escherichia coli BL21(DE3) using a maltose binding protein (MBP)-fused pMAL-c2x vector system containing the tobacco etch virus (TEV) proteolytic cleavage site. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides Re and Rg1 into (S)-Rg2 and (S)-Rh1, respectively, by hydrolyzing one glucose moiety attached to the C-20 position at pH 8.0 and 30°C. The Km values for p-nitrophenyl-β-d-glucopyranoside, Re, and Rg1 were 37.0 ± 0.4 μM and 3.22 ± 0.15 and 1.48 ± 0.09 mM, respectively, and the Vmax values were 33.4 ± 0.6 μmol min−1 mg−1 of protein and 19.2 ± 0.2 and 28.8 ± 0.27 nmol min−1 mg−1 of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM, followed by silica column purification, to produce (S)-Rh1 and (S)-Rg2 at chromatographic purities of 98% ± 0.5% and 97% ± 1.2%, respectively. This is the first report of gram-scale production of (S)-Rh1 and (S)-Rg2 from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3. PMID:23811513
Identification and characterization of a Mucilaginibacter sp. strain QM49 β-glucosidase and its use in the production of the pharmaceutically active minor ginsenosides (S)-Rh1 and (S)-Rg2.
Cui, Chang-Hao; Liu, Qing-Mei; Kim, Jin-Kwang; Sung, Bong-Hyun; Kim, Song-Gun; Kim, Sun-Chang; Im, Wan-Taek
Here, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) from Mucilaginibacter sp. strain QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity, bglQM, consists of 2,346 bp and is predicted to encode 781 amino acid residues. This enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed in Escherichia coli BL21(DE3) using a maltose binding protein (MBP)-fused pMAL-c2x vector system containing the tobacco etch virus (TEV) proteolytic cleavage site. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides Re and Rg1 into (S)-Rg2 and (S)-Rh1, respectively, by hydrolyzing one glucose moiety attached to the C-20 position at pH 8.0 and 30°C. The Km values for p-nitrophenyl-β-d-glucopyranoside, Re, and Rg1 were 37.0 ± 0.4 μM and 3.22 ± 0.15 and 1.48 ± 0.09 mM, respectively, and the Vmax values were 33.4 ± 0.6 μmol min(-1) mg(-1) of protein and 19.2 ± 0.2 and 28.8 ± 0.27 nmol min(-1) mg(-1) of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM, followed by silica column purification, to produce (S)-Rh1 and (S)-Rg2 at chromatographic purities of 98% ± 0.5% and 97% ± 1.2%, respectively. This is the first report of gram-scale production of (S)-Rh1 and (S)-Rg2 from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3. PMID:23811513
Role of epidermal γδ T-cell-derived interleukin 13 in the skin-whitening effect of Ginsenoside F1.
Han, Jiyeon; Lee, Eunkyung; Kim, EunJoo; Yeom, Myung Hun; Kwon, Ohsang; Yoon, Tae Hong; Lee, Tae Ryong; Kim, Kwangmi
Ginsenoside F1 (GF1) is a metabolite of ginsenoside Rg1. Although GF1 has several benefits for skin physiology, the effect of GF1 on skin pigmentation has not been reported. We found that a cream containing 0.1% GF1 showed a significant whitening effect on artificially tanned human skin after 8 weeks of application. However, GF1 did not inhibit mRNA expression of tyrosinase or dopachrome tautomerase (DCT) in normal human epidermal melanocytes (NHEMs) or cocultured NHEMs/normal human epidermal keratinocytes. Interestingly, GF1 enhanced production of interleukin 13 (IL-13) from human epidermal γδ T cells. IL-13 significantly reduced the mRNA expression and protein amount of both tyrosinase and DCT and reduced melanin synthesis activities in NHEMs, resulting in visible brightening of NHEM pellet. These results suggest that enhancement of IL-13 production by GF1 from epidermal γδ T cells might play a role in the skin-whitening effect of GF1 via the suppression of tyrosinase and DCT. PMID:25091975
Metabolism of ginsenoside Rb1 by human intestinal microflora and cloning of its metabolizing β-D-glucosidase from Bifidobacterium longum H-1.
Jung, Il-Hoon; Lee, Jeong Hoon; Hyun, Yang-Jin; Kim, Dong-Hyun
To understand the role of intestinal microflora in expressing the pharmacological effect of ginsenoside Rb1, the metabolic activity of ginsenoside Rb1 by 148 fecal specimens was measured and its metabolizing β-glucosidase was cloned. The average activities for p-nitrophenyl-β-D-glucopyranoside and ginsenoside Rb1 were 0.097±0.059 μmol/min/mg and 0.311±0.118 pmol/min/mg, respectively. These enzyme activities were not different between male and female, or between ages. A gene encoding β-D-glucosidase (BglX) was cloned from Bifidobacterium longum H-1, which transformed ginsenoside Rb1 to compound K. The probe for cloning was synthesized from the genes encoding a β-D-glucosidase of previously reported B. longum DJO10A. The sequences of the cloned gene revealed 2364 bp open reading frame (ORF) encoding a protein containing 787 amino acids (molecular weight of 95 kDa). The gene exhibited 99% homology (identities) to that of B. longum. The cloned gene was expressed under T7 promoter of the expression vector, pET-39b(+), in Escherichia coli BL21(DE3), and the expressed enzyme was purified by using HiTrap immobilized metal affinity chromatography (IMAC) HP. The enzyme potently biotransformed ginsenoside Rb1, loganin, arctiin and arbutin to ginsenoside Rd, loganetin, arctigenin and hydroquinone, respectively, but was not active in the case of hesperidin, and kakkalide. This is the first report on cloning and expression of β-D-glucosidase from B. longum. Based on these findings, ginsenoside Rb1 may be metabolized to bioactive compound(s) by exo-β-D-glucosidase(s) produced from the intestinal bacteria and its pharmacological effects may be dependent on intestinal bacterial exo-β-D-glucosidase(s) activity. PMID:22466563
Antiallergic activity of ginseng and its ginsenosides.
Choo, Min-Kyung; Park, Eun-Kyung; Han, Myung Joo; Kim, Dong-Hyun
In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley PMID:12865969
Evaluation of glucosidases of Aspergillus niger strain comparing with other glucosidases in transformation of ginsenoside Rb1 to ginsenosides Rg3
Chang, Kyung Hoon; Jo, Mi Na; Kim, Kee-Tae; Paik, Hyun-Dong
The transformation of ginsenoside Rb1 into a specific minor ginsenoside using Aspergillus niger KCCM 11239, as well as the identification of the transformed products and the pathway via thin layer chromatography and high performance liquid chromatography were evaluated to develop a new biologically active material. The conversion of ginsenoside Rb1 generated Rd, Rg3, Rh2, and compound K although the reaction rates were low due to the low concentration. In enzymatic conversion, all of the ginsenoside Rb1 was converted to ginsenoside Rd and ginsenoside Rg3 after 24 h of incubation. The crude enzyme (β-glucosidase) from A. niger KCCM 11239 hydrolyzed the β-(1→6)-glucosidic linkage at the C-20 of ginsenoside Rb1 to generate ginsenoside Rd and ginsenoside Rg3. Our experimental demonstration showing that A. niger KCCM 11239 produces the ginsenoside-hydrolyzing β-glucosidase reflects the feasibility of developing a specific bioconversion process to obtain active minor ginsenosides. PMID:24558310
[Simultaneous analysis of ginsenosides of various ginseng radix by HPLC].
Samukawa, K; Yamashita, H; Matsuda, H; Kubo, M
A simultaneous analysis of ginsenosides in Panax ginseng by high performance liquid chromatography recently established by us was applied to the analysis of various Ginseng Radix. The contents of ginsenosides in P. ginseng were examined according to the differences of the growth year, the used part of the plant, the method of processing and the cultivated location. In the case of P. ginseng cultivated in Nagano, Japan, the ratio (total ginsenosides content/total dry root weight) increases annually for three years. And it decreased at the fourth year and increases again at the fifth and the sixth years. Concerning the distribution of ginsenosides in the parts of the plant, they were contained at the highest level in a lateral root and in succession, in a rhizome > in a root hair > in a main root. They were also distributed much richer at periderm than at phloem or at xylem of a main root. The contents of panaxadiol- and panaxatriol-saponins gradually increase with the growth year, whereas an oleananesaponin, ginsenoside-Ro, drastically increases at the sixth year and goes to 15-fold, which suggests that the content of ginsenoside-Ro needs to be estimated much more when Ginseng Radix is evaluated. The fact that the processing for preparation of Red Ginseng increases the total content of saponins was clearly revealed by the present study. The highest contents of saponins among Red Ginsengs (all 6-year-old) were observed in ones prepared in Korea, and in Japan > in China, successively. PMID:7738782
Ginsenoside Rd and ischemic stroke; a short review of literatures☆
Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad
Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821
Simultaneous determination of three alkaloids, four ginsenosides and limonin in the plasma of normal and headache rats after oral administration of Wu-Zhu-Yu decoction by a novel ultra fast liquid chromatography-tandem mass spectrometry method: application to a comparative pharmacokinetics and ethological study.
Xu, Huarong; Li, Qing; Yin, Yidi; Lv, Chunxiao; Sun, Wanyang; He, Bosai; Liu, Ran; Chen, Xiaohui; Bi, Kaishun
A novel, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of eight main active ingredients (evodiamine, rutaecarpine, dehydroevodiamine, limonin, ginsenoside Rb1, Rd, Re and Rg1) in rat plasma after oral administration of Wu-Zhu-Yu (WZY) decoction, which is a celebrated and widely used Traditional Chinese Medicine formula for the treatment of headache. The analytes and internal standard (IS) were separated on a SHIM-PACK XR-ODS II column, and the detection was performed on a UFLC-MS/MS system with turbo ion spray source. The lower limits of quantification were 1.5, 0.5, 1.0, 2.0, 2.0, 1.0, 0.5 and 0.2 ng ml(-1) for evodiamine, rutaecarpine, dehydroevodiamine, limonin, gensenoside Rb1, Rd, Re and Rg1, respectively. Linearity, accuracy, precision and absolute recoveries of the eight analytes were all within satisfaction. The IS-normalized matrix factor was adopted for assessing the matrix effect and accompanied with a satisfactory result. The validated method has been successfully applied to compare pharmacokinetic profiles of the eight active ingredients in rat plasma between normal and headache rats after administration. Exact pharmaceutical effect of WZY decoction on headache was demonstrated by the ethological response of headache rats induced by nitric oxide donor after administration. The results indicated that the absorption of evodiamine, rutaecarpine, gensenoside Rb1, Re and Rg1 in headache group were significantly higher than those in normal group with similar concentration-time curves while no significant differences existed in limonin and ginsenoside Rd between the two groups. PMID:23584945
A Chimeric 18L1-45RG1 Virus-Like Particle Vaccine Cross-Protects against Oncogenic Alpha-7 Human Papillomavirus Types
Huber, Bettina; Schellenbacher, Christina; Jindra, Christoph; Fink, Dieter; Shafti-Keramat, Saeed; Kirnbauer, Reinhard
Persistent infection with oncogenic human papillomaviruses (HPV) types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr) mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC), a subset of cervical cancer (CxC). Although the incidence of cervical squamous cell carcinoma (SCC) has dramatically decreased following introduction of Papanicolaou (PAP) screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent) HPV vaccines comprise virus-like particles (VLP) of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7) includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18) targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1) of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1). Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent vaccine
Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction
NASA Astrophysics Data System (ADS)
Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin
Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.
Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction
Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin
Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care. PMID:26932472
Silver (Ι)-assisted enantiomeric analysis of ginsenosides using electrospray ionization tandem mass spectrometry.
Yu, Qing; Yu, Binbin; Yang, Hongmei; Li, Xue; Liu, Shuying
For identification of ginsenoside enantiomers, electrospray ionization mass spectrometry (ESI-MS) was used to generate silver complexes of the type [ginsenoside + Ag](+). Collision induced dissociation of the silver-ginsenoside complexes produced fragment ions by dehydration, allowing differentiation of ginsenoside enantiomers by the intensity of [M + Ag - H(2)O](+) ion. In the meanwhile, an approach based on the distinct profiles of enantiomer-selective fragment ion intensity varied with collision energy was introduced to refine the identification and quantitation of ginsenoside enantiomers. Five pairs of enantiomeric ginsenosides were distinguished and quantified on the basis of the distribution of fragment ion [M + Ag - H(2)O](+). This method was also extended to the identification of other type of ginsenoside isomers such as ginsenoside Rb2 and Rb3. For demonstrating the practicability of this novel approach, it was utilized to analyze the molar ratio of 20-(S) and 20-(R) type enantiomeric ginsenosides in enantiomer mixture in red ginseng extract. The generation of characteristic fragment ion [M + Ag - H(2)O](+) likely results from the reduction of potential energy barrier of dehydration because of the catalysis of silver ion. The mechanism of enantiomer identification of ginsenosides was discussed from the aspects of computational modeling and internal energy. PMID:23019162
Optimization of medium composition for keratinase production on feather by Bacillus licheniformis RG1 using statistical methods involving response surface methodology.
Ramnani, Priya; Gupta, Rani
A 3.5-fold increase in keratinase production by Bacillus licheniformis RG1 was achieved by using statistical methods involving Plackett-Burman design and response surface methodology. Eight variables were screened using Plackett-Burman design. Of these, glucose, peptone and glutathione were found to affect the response signal positively, whereas CaCl(2) had a negative effect. Further interaction of these factors, along with phosphate and incubation time, was studied using response surface methodology. An optimum keratinase production of 1295 units/mg dry weight was obtained with the following medium composition: 1% glucose, 1% peptone, 1% phosphate, 0.05% glutathione, 0.5% feather and 2% inoculum under shaking at 250 rev./min with an incubation period of 72 h at 37 degrees C. Keratinase production was found to be a function of biomass and maximum production occurred during the stationary phase. PMID:14871173
Identification of ginsenosides in roots of Panax ginseng by HPLC-APCI/MS.
Ma, Xiao-Qiong; Liang, Xin-Miao; Xu, Qing; Zhang, Xiao-Zhe; Xiao, Hong-Bin
A new HPLC-APCI/MS method for the identification of ginsenosides has been developed. The analyses were performed on a reversed-phase C18 column using a binary eluent (acetonitrile and water) under gradient conditions. Although APCI is a high-temperature evaporative process, HPLC-APCI/MS could effectively identify thermo-labile ginsenosides. The [M-H]- ions and the thermal degradation ions of ginsenosides could be clearly observed under negative and positive ion conditions, respectively, and these were used to identify the molecular masses, the aglycone structures and the sugar groups of ginsenosides. APCI/MS can provide more explicit information than ESI/MS for identifying and distinguishing ginsenosides. Using the HPLC-APCI/MS method, 35 ginsenosides were identified in Panax ginseng. PMID:15997851
Finding and Producing Probiotic Glycosylases for the Biocatalysis of Ginsenosides: A Mini Review.
Ku, Seockmo
Various microorganisms have been widely applied in nutraceutical industries for the processing of phytochemical conversion. Specifically, in the Asian food industry and academia, notable attention is paid to the biocatalytic process of ginsenosides (ginseng saponins) using probiotic bacteria that produce high levels of glycosyl-hydrolases. Multiple groups have conducted experiments in order to determine the best conditions to produce more active and stable enzymes, which can be applicable to produce diverse types of ginsenosides for commercial applications. In this sense, there are various reviews that cover the biofunctional effects of multiple types of ginsenosides and the pathways of ginsenoside deglycosylation. However, little work has been published on the production methods of probiotic enzymes, which is a critical component of ginsenoside processing. This review aims to investigate current preparation methods, results on the discovery of new glycosylases, the application potential of probiotic enzymes and their use for biocatalysis of ginsenosides in the nutraceutical industry. PMID:27196878
Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates.
Molnár, J; Szabó, D; Pusztai, R; Mucsi, I; Berek, L; Ocsovszki, I; Kawata, E; Shoyama, Y
In the present work a systematic study was initiated with crocine, ginsenoside and cannabinoid derivatives on multidrug resistant mouse lymphoma cells, viral tumor antigen expression and some human leukocyte functions. Among saffron derivatives, crocin and picrocrocin, triglucosyl and diglucosyl crocetin were ineffective on the reversal of multidrug resistance of lymphoma cells. Ginsenoside increased drug accumulation and tumor antigen expression at 2.0-20.0 micrograms/mL. Some cannabinoid derivatives such as cannabinol, cannabispirol and cannabidiol increased drug accumulation, while cannabidiolic acid, delta-9-THC and tetrahydro-cannabidiolic acid reduced drug accumulation of the human mdr1-gene transfected mouse lymphoma cells. The reversal of multidrug resistance is the result of the inhibition of the efflux pump function in the tumor cells. Crocetin esters were less potent than crocin itself in the inhibition of EBV early antigen expression. However crocin and diglucosylcrocetin inhibited early tumor antigen expression of adenovirus infected cells, but triglucosylcrocetin was less effective at 0.01-1.0 microgram/mL. The crocin had no antiviral effect [on HSV-2 infected vero cells] up to 25 micrograms/mL concentration. Ginsenosides had a moderate inhibitory effect except ginsenoside Rb1 (was the less effective) on the drug efflux pump. Among the cannabinoid derivatives the cannabinol and cannabispirol increased drug accumulation, while cannabidiolic acid and delta-8-THC, delta-9-THC and tetrahydro-cannabinol reduced drug accumulation in multidrug resistant mouse lymphoma cells. It is interesting that ginsenosides had a chemical structure-dependent immunomodulating effect by enhancing the activity of NK-cells and ADCC activities. PMID:10810367
Investigation of ginsenosides in different tissues after elicitor treatment in Panax ginseng
Oh, Ji Yeon; Kim, Yu-Jin; Jang, Moon-Gi; Joo, Sung Chul; Kwon, Woo-Saeng; Kim, Se-Yeong; Jung, Seok-Kyu; Yang, Deok-Chun
Background The effect of methyl jasmonate (MJ) on ginsenoside production in different organs of ginseng (Panax ginseng Meyer) was evaluated after the whole plant was dipped in an MJ-containing solution. MJ can induce the production of antioxidant defense genes and secondary metabolites in plants. In ginseng, MJ treatment in adventitious root resulted in the increase of dammarenediol synthase expression but a decrease of cycloartenol synthase expression, thereby enhancing ginsenoside biosynthesis. Although a previous study focused on the application of MJ to affect ginsenoside production in adventitious roots, we conducted our research on entire plants by evaluating the effect of exogenous MJ on ginsenoside production with the aim of obtaining new approaches to study ginsenoside biosynthesis response to MJ in vivo. Methods Different parts of MJ-treated ginseng plants were analyzed for ginsenoside contents (fine root, root body, epidermis, rhizome, stem, and leaf) by high-performance liquid chromatography. Results The total ginsenoside content of the ginseng root significantly increased after 2 d of MJ treatment compared with the control not subjected to MJ. Our results revealed that MJ treatment enhances ginsenoside production not in the epidermis but in the stele of the ginseng root, implying transportation of ginsenosides from the root vasculature to the epidermis. Application of MJ enhanced protopanaxadiol (PPD)-type ginsenosides, whereas chilling treatment induced protopanaxatriol (PPT)-type ginsenosides. Conclusion These findings indicate that the production of PPD-type and PPT-type ginsenosides is differently affected by abiotic and biotic stresses in the ginseng plant, and they might play different defense mechanism roles. PMID:25379007
Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis.
Zhang, Jun; Cao, Lijuan; Wang, Hong; Cheng, Xuefang; Wang, Lin; Zhu, Lin; Yan, Tingting; Xie, Yang; Wu, Yuzheng; Zhao, Min; Ma, Sijing; Wu, Mengqiu; Wang, Guangji; Hao, Haiping
Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-κB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NF-κB activation and restored the expression of PXR target genes in tumor necrosis factor-α-stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-κB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-κB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-κB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium-induced experimental colitis, which was associated with restored PXR/NF-κB signaling. This study indicates that ginsenosides may elicit anti-inflammatory effects via targeting PXR/NF-κB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-κB interaction in therapy for inflammatory bowel disease. PMID:25986850
Study on the noncovalent complexes of ginsenoside and cytochrome c by electrospray ionization mass spectrometry.
Zhang, Huarong; Ding, Lan; Qu, Chenling; Li, Dan; Zhang, Hanqi
The noncovalent complexes of cytochrome c and ginsenoside were studied by electrospray ionization mass spectrometry (ESI-MS). Ginsenoside Rb2 and Re were bound to cytochrome c to form several complexes with different stoichiometric relation. The 1:1 and 1:2 complexes of cytochrome c to ginsenoside were considered and the dissociation constants were obtained according to the intensities of cytochrome c and complexes when the concentrations of cytochrome c and ginsenoside have been known. Competition experiment was performed to validate the result. The K(D) values obtained with different reactive systems were consistent with each other. PMID:17324614
Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3
Song, Jae-Hyoung; Choi, Hwa-Jung; Song, Hyuk-Hwan; Hong, Eun-Hye; Lee, Bo-Ra; Oh, Sei-Ryang; Choi, Kwangman; Yeo, Sang-Gu; Lee, Yong-Pyo; Cho, Sungchan; Ko, Hyun-Jeong
Background Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of 100 μg/mL. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at 100 μg/mL. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection. PMID:25378991
Transgenic modification of gai or rg/1 causes dwarfing and alters gibberellins, root growth, and metabolite profiles in Populus
Tschaplinski, Timothy J; Busov, V.; Meilan, R; Pearce, D; Rood, s; Ma, C; Strauss, S
In Arabidopsis and other plants, gibberellin (GA)-regulated responses are mediated by proteins including GAI, RGA and RGL1-3 that contain a functional DELLA domain. Through transgenic modification, we found that DELLA-less versions of GAI (gai) and RGL1 (rgl1) in a Populus tree have profound, dominant effects on phenotype, producing pleiotropic changes in morphology and metabolic profiles. Shoots were dwarfed, likely via constitutive repression of GA-induced elongation, whereas root growth was promoted two- to threefold in vitro. Applied GA{sub 3} inhibited adventitious root production in wild-type poplar, but gai/rgl1 poplars were unaffected by the inhibition. The concentrations of bioactive GA{sub 1} and GA{sub 4} in leaves of gai- and rgl1-expressing plants increased 12- to 64-fold, while the C{sub 19} precursors of GA{sub 1} (GA{sub 53}, GA{sub 44} and GA{sub 19}) decreased three- to ninefold, consistent with feedback regulation of GA 20-oxidase in the transgenic plants. The transgenic modifications elicited significant metabolic changes. In roots, metabolic profiling suggested increased respiration as a possible mechanism of the increased root growth. In leaves, we found metabolite changes suggesting reduced carbon flux through the lignin biosynthetic pathway and a shift towards allocation of secondary storage and defense metabolites, including various phenols, phenolic glucosides, and phenolic acid conjugates.
Ginsenoside-Rg{sub 1} induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a
Kwok, Hoi-Hin; Chan, Lai-Sheung; Poon, Po-Ying; Yue, Patrick Ying-Kit; Wong, Ricky Ngok-Shun
Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg{sub 1} (Rg{sub 1}), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg{sub 1}-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg{sub 1} could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a. Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3′-UTR. Intriguingly, ginsenoside-Rg{sub 1} was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg{sub 1}-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg{sub 1} could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg{sub 1,} and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy. - Highlights: • Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. • Ginsenoside-Rg{sub 1} (Rg{sub 1}) has been demonstrated as an angiogenesis-stimulating compound. • We found that Rg{sub 1} induces angiogenesis by
Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin
Im, Dong-soon; Nah, Seung-yeol
Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic mediator. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs. PMID:24122014
Red ginseng extract promotes the hair growth in cultured human hair follicles.
Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun
Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716
Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles
Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun
Abstract Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716
Selection of high ginsenoside producing ginseng hairy root lines using targeted metabolic analysis.
Woo, Sung-Sick; Song, Ji-Sook; Lee, Ju-Yeon; In, Dong Su; Chung, Hwa-Jee; Liu, Jang Ryol; Choi, Dong-Woog
To develop an experimental system for studying ginsenoside biosynthesis, we generated thousands of ginseng (Panax ginseng C.A. Meyer) hairy roots, genetically transformed roots induced by Agrobacterium rhizogenes, and analyzed the ginsenosides in the samples. 27 putative ginsenosides were detected in ginseng hairy roots. Quantitative and qualitative variations in the seven major ginsenosides were profiled in 993 ginseng hairy root lines using LC/MS and HPLC-UV. Cluster analysis of metabolic profiling data enabled us to select hairy root lines, which varied significantly in ginsenoside production. We selected hairy root lines producing total ginsenoside contents 4-5 times higher than that of a common hairy root population, as well as lines that varied in the ratio of the protopanaxadiol to protopanaxatriol type ginsenoside. Some of the hairy root lines produce only a single ginsenoside in relatively high amounts. These metabolites represent the end product of gene expression, thus metabolic profiling can give a broad view of the biochemical status or biochemical phenotype of a hairy root line that can be directly linked to gene function. PMID:15474561
Anti-breast cancer activity of Fine Black ginseng (Panax ginseng Meyer) and ginsenoside Rg5
Kim, Shin-Jung; Kim, An Keun
Background Black ginseng (Ginseng Radix nigra, BG) refers to the ginseng steamed for nine times and fine roots (hairy roots) of that is called fine black ginseng (FBG). It is known that the content of saponin of FBG is higher than that of BG. Therefore, in this study, we examined antitumor effects against MCF-7 breast cancer cells to target the FBG extract and its main component, ginsenoside Rg5 (Rg5). Methods Action mechanism was determined by MTT assay, cell cycle assay and western blot analysis. Results The results from MTT assay showed that MCF-7 cell proliferation was inhibited by Rg5 treatment for 24, 48 and 72 h in a dose-dependent manner. Rg5 at different concentrations (0, 25, 50 and 100 μM), induced cell cycle arrest in G0/G1 phase through regulation of cell cycle-related proteins in MCF-7 cells. As shown in the results from western blot analysis, Rg5 increased expression of p53, p21WAF1/CIP1 and p15INK4B and decreased expression of Cyclin D1, Cyclin E2 and CDK4. Expression of apoptosis–related proteins including Bax, PARP and Cytochrome c was also regulated by Rg5. These results indicate that Rg5 stimulated cell apoptosis and cell cycle arrest at G0/G1 phase via regulation of cell cycle-associated proteins in MCF-7 cells. Conclusion Rg5 promotes breast cancer cell apoptosis in a multi-path manner with higher potency compared to 20(S)-ginsenoside Rg3 (Rg3) in MCF-7 (HER2−/ER+) and MDA-MB-453 (HER2+/ER−) human breast cancer cell lines, and this suggests that Rg5 might be an effective natural new material in improving breast cancer. PMID:26045685
[Autotoxic effect of ginsenoside extrats on growth of American ginseng in different medium].
Jiao, Xiao-lin; Bi, Xiao-bao; Zhang, Xue-song; Gao, Wei-wei
Ginsenosides are the abundant secondary metabolites in American ginseng (Panax quinquefolium), it could be released into soil through root exudation and decomposition during plant growth. This study determined ginsenoside contents in American ginseng cultivated soil by HPLC. Three ginsenosides, Rb1, Rb2 and Rd, were detected in the rhizosphere soil of 3-4 years old American ginseng cultivated in Huairou District, Beijing, and their contents were 0.80-3.19 mg x kg(-1). Correspondingly, the contents of the three ginsenosides in soil solution were 4-16 mg x L(-1) at field water-holding capacity of 20%. According to the field soil test data, we designed the concentration of ginsenosides for bioassays (0.2-125 mg x L(-1) in solution or 0.2-125 mg x kg(-1) in soil). The results showed that radicle lengths of American ginseng were reduced by 6%-23% in solution containing 0.2-125 mg x L(-1) ginsenoside extract, and a significant difference was observed at concentration of 125 mg x L(-1) (P < 0.05). The shoot lengths of American ginseng were not significantly inhibited by 0.2-125 mg x L(-1) ginsenosides extractions. After 20 days of growth in nutrient solution amended with 25 mg x L(-1) ginsenosides extraction, plant height of 3-year-old American ginseng seedling was decreased by 28% compared to the control, and the biomass of aerial parts was also reduced by 50% (P < 0.05). However, the growth of newly-grown fibrous root was not significantly inhibited. Comparatively, when American ginseng embryos were cultivated into sterile or non-sterile soil, neither radicle lengths nor shoot lengths were significantly affected by 0.2-125 mg x kg(-1) ginsenoside extracts. In conclusion, ginsenosides showed autotoxic effect on growth of American ginseng radicle and adult seedling, however, this effect was weakened in field soil. PMID:26281575
Alam, Hasan B.
This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683
Inhibitory effect of ginsenosides from steamed ginseng-leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells.
Tung, Nguyen Huu; Quang, Tran Hong; Son, Jeong-Hyun; Koo, Jung-Eun; Hong, Hye-Jin; Koh, Young-Sang; Song, Gyu Yong; Kim, Young Ho
Interleukin-12, a heterodimeric cytokine comprising p40 and p35 subunits, plays an essential role in the regulating the differentiation of Th cells, which establish and maximize the capabilities of the immune system. The aim of present study is to screen the effect of 21 ginsenosides from steamed ginseng-leaves and flowers on IL-12 production in bone marrow-derived dendritic cells induced by lipopolysaccharide. Noticeably, ginsenoside Rg(6) (12) and ginsenoside F(4) (13) exhibited particularly inhibitory effect on LPS-induced IL-12 production with the inhibition values of 80 and 82%; and ginsenoside ST(1) (4), ginsenoside SL(2) (8), ginsenoside SL(3) (9), ginsenoside Rh(3) (14), ginsenoside Rk(2) (15), and ginsenoside Rs(4) (18) showed moderate effects with inhibition rates of 63, 65, 67, 68, 71, 73, and 67%, respectively. These results warrant further studies concerning potential of saponin extracts of steamed ginseng-leaves and flowers for medicinal uses. PMID:21544734
Analgesic Effect of Intrathecal Ginsenosides in a Murine Bone Cancer Pain
Kim, Woong Mo; Lee, Hyung Gon; Choi, Jeong Il; Kim, Yeo Ok; Song, Ji A
Background Bone cancer pain has a disruptive effect on the cancer patient's quality of life. Although ginsenosides have been used as traditional medicine in Eastern Medicine, the effect on bone cancer pain has not been thoroughly studied. The aim of this study was to determine whether ginsenosides may alter the bone cancer pain at the spinal level. Methods NCTC 2472 tumor cells (2.5 × 105) were injected into the femur of adult male C3H/HeJ mice to evoke bone tumor and bone cancer pain. To develop bone tumor, radiologic pictures were obtained. To assess pain, the withdrawal threshold was measured by applying a von Frey filament to the tumor cells inoculation site. The effect of intrathecal ginsenosides was investigated. Effect of ginsenosides (150, 500, 1,000 µg) was examined at 15, 30, 60, 90, 120 min after intrathecal delivery. Results The intrafemoral injection of NCTC 2472 tumor cells induced a radiological bone tumor. The withdrawal threshold with tumor development was significantly decreased compared to the sham animals. Intrathecal ginsenosides effectively increased the withdrawal threshold in the bone cancer site. Conclusions NCTC 2472 tumor cells injection into the mice femur caused bone tumor and bone cancer pain. Intrathecal ginsenosides attenuated the bone cancer-related pain behavior. Therefore, spinal ginsenosides may be an alternative analgesic for treating bone cancer pain. PMID:21217885
Protective Effect of Ginsenoside R0 on Anoxic and Oxidative Damage In vitro.
Jiang, Zhou; Wang, Yuhui; Zhang, Xiaoyun; Peng, Tao; Li, Yanqing; Zhang, Yi
To examine the neuroprotective effects of ginsenoside R0, we investigated the effects of ginsenoside R0 in PC12 cells under an anoxic or oxidative environment with Edaravone as a control. PC12 neuroendocrine cells were used as a model target. Anoxic damage or oxidative damage in PC12 cells were induced by adding sodium dithionite or hydrogen peroxide respectively in cultured medium. Survival ratios of different groups were detected by an AlamarBlue assay. At the same time, the apoptosis of PC12 cells were determined with flow cytometry. The putative neuroprotective effects of ginsenoside R0 is thought to be exerted through enhancing the activity of antioxidant enzymes Superoxide dismutases (SOD). The activity of SOD and the level of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), were measured to evaluate the protective and therapeutic effects of ginsenoside R0. Ginsenoside R0 treated cells had a higher SOD activity, lower MDA level and lower ROS, and their survival ratio was higher with a lower apoptosis rate. It is suggested that ginsenoside R0 has a protective effect in the cultured PC12 cells, and the protection efficiency is higher than Edaravone. The protective mechanisms of these two are different. The prevent ability of ginsenoside R0 is higher than its repair ability in neuroprotection in vitro. PMID:24009848
Neuroprotective effects of ginsenoside Rb1 on hippocampal neuronal injury and neurite outgrowth
Liu, Juan; He, Jing; Huang, Liang; Dou, Ling; Wu, Shuang; Yuan, Qionglan
Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta (25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta (25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta (25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta (25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta (25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling. PMID:25206916
Ginsenoside Rg3 attenuated omethoate-induced lung injury in rats.
Wang, J; Yu, X F; Zhao, J J; Shi, S M; Fu, L; Sui, D Y
Organophosphorus exposure affects different organs such as the lung, gastrointestinal tract, liver, and brain. The present experiment aimed to evaluate the effect of ginsenoside Rg3 on lung injury induced by acute omethoate poisoning. Rats were administered with omethoate subcutaneously at a single dose of 60 mg/kg, followed by ginsenoside Rg3 (5, 10, or 20 mg/kg) treatment. Histopathological examination of the lung was performed at 24 h after the omethoate exposure. The antioxidative parameters in the lung were also assayed. Moreover, the activities of acetylcholinesterase, myeloperoxidase, and the content of tumor necrosis factor α (TNF-α) in the lung were determined. The results showed that ginsenoside Rg3 attenuated omethoate-induced lung injury. Ginsenoside Rg3 increased the level of glutathione in the lung (p < 0.05 or p < 0.01). The altered activities of superoxide dismutase and catalase in the lung were also ameliorated by ginsenoside Rg3 treatment (p < 0.05 or p < 0.01). Ginsenoside Rg3 caused significant reductions in the contents of malondialdehyde, TNF-α, and the activity of myeloperoxidase (p < 0.05 or p < 0.01). The present study demonstrated that ginsenoside Rg3 had a protective effect against omethoate-induced lung injury in rats, and the mechanisms were related to its antioxidant potential and anti-inflammatory effect. PMID:26240163
Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury
Wang, Baogang; Zhu, Qingsan; Man, Xiaxia; Guo, Li; Hao, Liming
Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-dependently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reperfusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression. PMID:25374589
Ginsenoside-Rg5 induces apoptosis and DNA damage in human cervical cancer cells
Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside-Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside-Rg5 had any marked cytotoxic, apoptotic or DNA-damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT-3) were used to investigate the cytotoxicity of ginsenoside-Rg5 using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside-Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of γH2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside-Rg5 treatment compared with the C-33A, HT-3 and Me180 cells. As expected, ginsenoside-Rg5 induced significant concentration- and time-dependent increases in apoptosis. In addition, ginsenoside-Rg5 induced significant concentration-dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of γH2AX-positive HeLa and MS751 cells also revealed that ginsenoside-Rg5 caused DNA double-strands to break in a concentration-dependent manner. In conclusion, ginsenoside-Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer. PMID:25355274
Bioactivity and Bioavailability of Ginsenosides Are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing
Niu, Tao; Smith, Diane; Yang, Zhen; Gao, Song; Yin, Taijun; Jiang, Zhi-Hong; You, Ming; Gibbs, Richard A.; Petrosino, Joseph F.; Hu, Ming
Purpose The ability of bacteria in the intestinal microbiome to convert naturally occurring primary ginsenosides in red ginseng extract or RGE to active secondary ginsenosides was investigated. Methods The anti-proliferative activity of ginsenosides was tested using the mouse lung cancer LM1 cells. Their permeabilities were evaluated in Caco-2 cell monolayers. Systemic exposure of secondary ginsenosides was determined in A/J mice. 16S rRNA gene pyrosequencing was used to determine membership and abundance of bacteria in the intestinal microbiome. Results Secondary ginsenoside C-K exhibited higher anti-proliferative activity and permeability than primary ginsenosides, and significant amounts of secondary ginsenosides (F2 and C-K) were found in the blood of A/J mice following oral administration of the primary ginsenoside Rb1. Because mammalian cells did not hydrolyze ginsenoside, we determined the ability of bacteria to hydrolyze ginsenosides and found that the primary ginsenoside Rb1 underwent stepwise hydrolysis to Rd, F2, and then C-K. Formation of F2 from Rd was the rate-limiting step in the biotransformation of Rb1 to C-K. Conclusion This is the first study to characterize the A/J mouse intestinal microbiome and reveal the presence of certain bacterial families capable of efficiently converting inactive primary ginsenosides to active secondary ginsenosides in vivo. PMID:23254888
Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics.
Ma, Li-Yuan; Zhang, You-Bo; Zhou, Qi-Le; Yang, Yan-Fang; Yang, Xiu-Wei
A high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg₁ (1); 20(S)-ginsenoside Rh₁ (2); 20(S)-ginsenoside Rg₂ (3); 20(R)-ginsenoside Rh₁ (4); 20(R)-ginsenoside Rg₂ (5); ginsenoside Rd (6); 20(S)-ginsenoside Rg₃ (7); and 20(R)-ginsenoside Rg₃ (8) in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL) at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long tmax values, suggesting that they were slowly absorbed, while the ginsenosides 1-5, belonging to protopanaxatriol-type saponins, had different tmax values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t1/2 of 20(S)-epimers were always longer than those of 20(R)-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL. PMID:26633350
The potential of minor ginsenosides isolated from the leaves of Panax ginseng as inhibitors of melanogenesis.
Lee, Dae-Young; Cha, Byeong-Ju; Lee, Young-Seob; Kim, Geum-Soog; Noh, Hyung-Jun; Kim, Seung-Yu; Kang, Hee Cheol; Kim, Jin Hee; Baek, Nam-In
Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2) and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax ginseng. The chemical structures were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%, respectively, at a concentration of 80 µM. Likewise, the three compounds showed inhibitory activity on body pigmentation on a zebrafish model, which is commonly used as a model for biomedical or cosmetic research. These results from in vitro and in vivo systems suggest that the three aforementioned compounds isolated from Panax ginseng may have potential as new skin whitening compounds. PMID:25590297
The Potential of Minor Ginsenosides Isolated from the Leaves of Panax ginseng as Inhibitors of Melanogenesis
Lee, Dae-Young; Cha, Byeong-Ju; Lee, Young-Seob; Kim, Geum-Soog; Noh, Hyung-Jun; Kim, Seung-Yu; Kang, Hee Cheol; Kim, Jin Hee; Baek, Nam-In
Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2) and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax ginseng. The chemical structures were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%, respectively, at a concentration of 80 µM. Likewise, the three compounds showed inhibitory activity on body pigmentation on a zebrafish model, which is commonly used as a model for biomedical or cosmetic research. These results from in vitro and in vivo systems suggest that the three aforementioned compounds isolated from Panax ginseng may have potential as new skin whitening compounds. PMID:25590297
Effect of gamma irradiation on the conversion of ginsenoside Rb1 to Rg3
NASA Astrophysics Data System (ADS)
Kim, Jae-Hun; Kwon, Sun-Kyu; Sung, Nak-Yun; Jung, Pil-Mun; Choi, Jong-il; Kim, Jae-Kyung; Sharma, Arun K.; Lee, Ju-Woon
Ginsenosides, the most important secondary metabolites in ginseng, have various biological activities. Many studies have focused on the conversion of one of the major ginsenosides, Rb1, to the more active minor ginsenoside, Rg3. This study was carried out to investigate the effect of gamma irradiation on the conversion of Rb1 to Rg3. Rb1 solutions were gamma-irradiated at doses of 10 and 30 kGy and analyzed by high performance liquid chromatography (HPLC). HPLC chromatograms showed a decreased content of Rb1 with increasing irradiation dose, but the content of Rg3 was increased. The highest content of Rg3 was present in the 30 kGy-irradiated Rb1 sample. The cytotoxic effects tested in cancer cell lines were increased in the gamma-irradiated group. Therefore, these results suggest that gamma irradiation can be an effective method for the conversion of the ginsenoside Rb1 to Rg3.
Fast determination of total ginsenosides content in ginseng powder by near infrared reflectance spectroscopy
NASA Astrophysics Data System (ADS)
Chen, Hua-cai; Chen, Xing-dan; Lu, Yong-jun; Cao, Zhi-qiang
Near infrared (NIR) reflectance spectroscopy was used to develop a fast determination method for total ginsenosides in Ginseng (Panax Ginseng) powder. The spectra were analyzed with multiplicative signal correction (MSC) correlation method. The best correlative spectra region with the total ginsenosides content was 1660 nm~1880 nm and 2230nm~2380 nm. The NIR calibration models of ginsenosides were built with multiple linear regression (MLR), principle component regression (PCR) and partial least squares (PLS) regression respectively. The results showed that the calibration model built with PLS combined with MSC and the optimal spectrum region was the best one. The correlation coefficient and the root mean square error of correction validation (RMSEC) of the best calibration model were 0.98 and 0.15% respectively. The optimal spectrum region for calibration was 1204nm~2014nm. The result suggested that using NIR to rapidly determinate the total ginsenosides content in ginseng powder were feasible.
Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress-mediated c-Jun N-terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease.
Mu, Jun-Shan; Lin, Hang; Ye, Jian-Xin; Lin, Min; Cui, Xiao-Ping
The neuroprotective agents currently used to treat Alzheimer's disease (AD) often only target one aspect of the disease process. Therefore, identifying effective drug targets associated with the pathogenesis of AD is critical for the production of novel AD therapeutic strategies. The present study aimed to investigate the underlying mechanisms of the neuroprotective effects of Rg1 on a rat model of AD. A double transgenic β‑amyloid (Aβ) precursor protein/PS1 rat model was established, which co‑expressed mutations associated with AD. Aβ plaques and neurofibrillary tangles (NFTs) were detected by immunohistochemistry. The detection of the protein expression levels of caspase‑3 and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling (TUNEL) staining were used to determine the level of apoptosis in the brain tissue. The expression levels of the endoplasmic reticulum (ER) stress biomarker, glucose‑regulated protein 78 (Grp78), and the mitochondrial apoptosis biomarkers, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), were analyzed by western blotting. Furthermore, the expression of the proteins associated with the ER stress unfolded protein response (UPR) was determined, in order to examine the levels of ER stress. The mRNA expression of downstream genes of UPR were also detected by reverse transcription‑polymerase chain reaction. The protein expression levels of the apoptosis‑associated phosphorylated‑c‑Jun N‑terminal protein kinase (p‑JNK), caspase‑12 and cAMP response element‑binding transcription factor homologous protein were determined by western blotting. The results of the present study indicated that the accumulation of NFTs and Aβ plaques was significantly decreased in the Rg1‑treated AD rats, compared with untreated AD rats. The expression of caspase‑3 and the number of TUNEL‑positive cells were also significantly decreased in the Rg1‑treated rats, as compared with the AD rats
Antioxidative properties of ginsenoside Ro against UV-B-induced oxidative stress in human dermal fibroblasts.
Kang, Hyun Ji; Oh, Yuri; Lee, Sihyeong; Ryu, In Wang; Kim, Kyunghoon; Lim, Chang-Jin
Ginsenoside Ro (Ro), an oleanolic acid-type ginsenoside, exhibited suppressive activities on reactive oxygen species (ROS) and matrix metalloproteinase-2 (MMP-2) elevation in UV-B-irradiated fibroblasts. Ro could overcome the reduction of the total glutathione (GSH) contents in UV-B-irradiated fibroblasts. Ro could not interfere with cell viabilities in UV-B-irradiated fibroblasts. Collectively, Ro possesses a potential skin anti-photoaging property against UV-B radiation in fibroblasts. PMID:26214051
Structural Characterization of Ginsenosides from Flower Buds of Panax ginseng by RRLC-Q-TOF MS.
Wu, Wei; Lu, Ziyan; Teng, Yaran; Guo, Yingying; Liu, Shuying
Ginseng flower bud as a part of Panax ginseng has received much attention as a valuable functional food with medicinal potential. A few studies focused on systematic and comprehensive studies on its major ingredients. This study aims to rapidly characterize ginsenosides in ginseng flower buds and provide scientific basis for developing functional food, exploiting pharmaceutical effects and making full use of ginseng resources. A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for rapid qualitative and quantitative analysis of ginsenosides in ginseng flower buds. The compounds were identified by comparing retention time of the reference standards, accurate mass measurement and the fragment ions obtained from RRLC-Q-TOF-MS/MS analyses. A total of 14 kinds of ginsenosides were identified and 5 kinds of malonyl-ginsenosides were first tentatively identified in ginseng flower buds. Ten kinds of main ginsenosides were quantitatively analyzed. The developed RRLC-Q-TOF-MS method was demonstrated as an effective analytical means for rapid characterization of the ginsenosides in flower buds of P. ginseng. The research result is valuable for quality control, assessment of authenticity and stability evaluation of ginseng flower buds. PMID:26270079
Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells.
Li, Na; Liu, Bin; Dluzen, Dean E; Jin, Yi
We investigated the effect of ginsenoside Rg2 on neurotoxic activities induced by glutamate in PC12 cells. The cells were incubated with glutamate (1 mmol/L), glutamate and ginsenoside Rg2 (0.05, 0.1, 0.2 mmol/L) or nimodipine (5 micromol/L) for 24 h. The cellular viability was assessed by MTT assay. The lipid peroxidation products malondialdehyde (MDA) and nitrogen oxide (NO) were measured by a spectrophotometric method. Fura-2/AM, as a cell permeable fluorescent probe for Ca2+, was used to detect intracellular Ca2+ concentration ([Ca2+]i) using a monespectrofluorometer. Immunocytochemical techniques were employed to check the protein expression levels of calpain II, caspase-3 and beta-amyloid (Abeta)1-40 in PC12 cells. The results showed that glutamate decreased the cell viability, increased [Ca2+]i, lipid peroxidation (the excessive production of MDA, NO) and the protein expression levels of calpain II, caspase-3 and Abeta1-40 in PC12 cells. Ginsenoside Rg2 significantly attenuated glutamate-induced neurotoxic effects upon these parameters at all doses tested. Our study suggests that ginsenoside Rg2 has a neuroprotective effect against glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis. In addition, the inhibitory effect of ginsenoside Rg2 against the formation of Abeta1-40 suggests that ginsenoside Rg2 may also represent a potential treatment strategy for Alzheimer's disease. PMID:17257792
Red American Ginseng: Ginsenoside Constituents and Antiproliferative Activities of Heat-Processed Panax quinquefolius Roots
Wang, Chong-Zhi; Aung, Han H.; Ni, Ming; Wu, Ji-An; Tong, Robin; Wicks, Sheila; He, Tong-Chuan; Yuan, Chun-Su
Red Asian ginseng (Panax ginseng C. A. Meyer, Araliaceae) is used in many Oriental countries. In this study, the saponin constituents and anticancer activities of steamed American ginseng (Panax quinquefolius L.) roots were evaluated. The contents of 12 ginsenosides in the roots were determined using high performance liquid chromatography (HPLC). After the steaming treatment (100 – 120 °C for 1 h and 120 °C for 0.5 – 4 h), the quantity of 7 ginsenosides decreased and that of 5 others increased. The content of ginsenoside Rg3, a previously recognized anticancer compound, increased significantly when the root was steamed at 120 °C for 0.5 – 3 h. The antiproliferative effects of unsteamed and steamed (120 °C for 1 h and 2 h) American ginseng root extracts were assayed by the modified trichrome stain (MTS) method using three cancer cell lines (SW-480, HT-29, NSCLC). Heat-processing increased the antiproliferative effect of American ginseng significantly, and the activity of the extract from roots steamed for 2 h was greater than that of roots steamed for 1 h. Chemical constituents and antiproliferative activities of white and red Asian ginseng have also been evaluated. Five representative ginsenosides, Rb1, Rd, Re, Rg2 and Rg3, were studied. Ginsenoside Rg3 had the most potent effect. The antiproliferative activities of red American ginseng are augmented when ginsenoside Rg3 is increased. PMID:17538869
Liquid chromatography/mass spectrometry of malonyl-ginsenosides in the authentication of ginseng.
Kite, Geoffrey C; Howes, Melanie-Jayne R; Leon, Christine J; Simmonds, Monique S J
Different negative ion electrospray (ES) source conditions are required to concentrate the ion current in [M-H](-) for malonylated and non-malonylated ginsenosides. However, both can be ionised optimally in a single liquid chromatography/mass spectrometry (LC/MS) analysis by employing switchable voltages in the post-source ion optics of a quadrupole ion trap mass spectrometer. Coupled with automatic MS/MS scanning and post-acquisition neutral loss data analysis, this method provides a means of profiling the malonylated and acetylated ginsenosides in ginseng extracts. Analyses revealed numerous malonylated ginsenosides that could be partially characterised by serial MS/MS experiments. The ratio of mRb(1) to other isomeric forms present and to mRb(2) and mRc appears to show consistent differences among Panax ginseng (Asian ginseng), P. quinquefolius (American ginseng) and P. notoginseng (Sanchi ginseng). The ratio of malonylated to non-malonylated ginsenosides is reduced in the red form of Asian ginseng compared with the white form and there is a concomitant increase in the levels of the corresponding acetylated ginsenosides. The ability to analyse malonylated ginsenosides is an important contribution to the range of chemical characteristics that can be used to authenticate the different species of ginseng and will assist in quality control and standardisation. PMID:12539190
Four new ginsenosides from red ginseng with inhibitory activity on melanogenesis in melanoma cells.
Zhou, Qi-Le; Yang, Xiu-Wei
During a search for novel melanogenesis inhibitors originating from nature sources, four new ginsenosides, including three dammarane-type triterpenoid saponins, 20(S)-ginsenoside-Rf-1a (1), 20Z-ginsenoside-Rs4 (2), 23-O-methylginsenoside-Rg11 (3), and one oleanane-type saponin, ginsenoside-Ro-6'-O-butyl ester (4) were isolated from red ginseng (the steamed ginseng) to evaluate their protective effects against melanogenesis. Compounds 2 and 3 exhibited potent inhibitory effects against both melanin synthesis and tyrosinase activity in a dose-dependent manner in the α-MSH-stimulated B16 melanoma cells, and were more potent than the positive control arbutin, a well-known tyrosinase inhibitor. The results indicated that just the two carbon-20(22) double-bond-type ginsenosides showed strong inhibiting activity on melanogenesis through reducing tyrosinase activity. Thus, ginsenosides with such similar chemical structure in red ginseng may be potential natural products as tyrosinase inhibitors against malignant melanoma. PMID:26087936
Ethosomes and Transfersomes for Topical Delivery of Ginsenoside Rhl from Red Ginseng: Characterization and In Vitro Evaluation.
Choi, Jae-Hwan; Cho, Sun-Hang; Yun, Je-Jung; Yu, Young-Beob; Cho, Cheong-Weon
Red ginseng (the steamed root of Panax ginseng C. A. Mayer), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Ginsenoside Rhl, a bacterial metabolite of ginsenoside Rgl, is a protopanaxatriol type of ginsenosides. Liposomes do not deeply penetrate the skin and remain confined to the stratum corneum.Thus, new vesicular colloidal carriers such as ethosomes and transfersomes have been developed as an enhanced type of liposomes, recently. The aim of this study was to improve the topical delivery of ginsenoside Rhl isolated from red ginseng employing new vesicular system of ethosomes and transfersomes compared to conventional liposome. Characterization of ginsenoside Rhl-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (% EE), and transmission electron microscopy (TEM) studies. In addition, skin permeation profile was obtained using frantz diffusion cells and rat dorsal skin treated with ethosome and transfersome compared with conventional iposome. The size of vesicles range from 108.5 to 322.9 nm, and negatively charged from -20.95 to -31.37 mV. The % EE of ginsenoside Rh1 was obtained between 45.0 to 65.0%. Transfersomes provided a significantly higher skin permeation of ginsenoside Rhl compared to ethosome and conventional liposome. Therefore, based on the current study, ginsenoside Rhl-loaded transfersomes can act as a topical therapeutic effects potential. PMID:26369134
[Analysis of ginsenosides by high performance liquid chromatography/mass spectrometry/mass spectrometry(LC/MS/MS)].
Xü, Z X; Xiao, H B; Wang, J N; Liang, X M
Ginseng, one of the most popular medicinal herbs used in traditional Chinese medicines, has been studied to have biological effects attributing to its main constituents such as ginsenosides. There are more than 30 kinds of ginsenosides and some of them have similar polarity and structure. Thus, it is difficult to separate those ginsenosides with isocratic mobile phase owing to their similar polarity. A reversed-phase high performance liquid chromatographic method with gradient elution has been developed in this work. Nine ginsenosides can be separated by this method. Among them, five ginsenosides with different molecular weights can be determined by means of their molecular weight gained through LC/MS with an ESI interface. Re and Rd have the same Mw but belonging to two different kinds of ginsenosides. They can be differentiated from each other through their MS/MS gained by CID(collision induced decomposition) at the second stage quadrapole. Rc and Rb3 having the same molecular weight and belonging to the same kind of ginsenoside can be distinguished through their negative ion spectra gotten from LC/MS. So 9 ginsenosides can be determined by LC/MS/MS. This method can also be used to determine the ginsenosides contained in commercially available samples. PMID:12541739
Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury
Liu, Yang; Zhang, Ren-Yu; Zhao, Jun; Dong, Zheng; Feng, Dong-Yun; Wu, Rui; Shi, Ming; Zhao, Gang
Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM), showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation. PMID:26114390
Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury.
Liu, Yang; Zhang, Ren-Yu; Zhao, Jun; Dong, Zheng; Feng, Dong-Yun; Wu, Rui; Shi, Ming; Zhao, Gang
Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM), showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation. PMID:26114390
Antitumoral Activity of (20R)- and (20S)-Ginsenoside Rh2 on Transplanted Hepatocellular Carcinoma in Mice.
Lv, Qun; Rong, Na; Liu, Li-Jia; Xu, Xiao-Lin; Liu, Jian-Ting; Jin, Feng-Xie; Wang, Chun-Mei
Hepatocellular carcinoma is one of the leading causes of malignancy-related death in China. Its therapy in clinics is a big challenge. Ginsenoside Rh2 is one of the most notable cancer-preventing components from red ginseng and it has been reported that ginsenoside Rh2 exhibited potent cytotoxicity against human hepatoma cells. Rh2 exists as two different stereoisomeric forms, (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2. Previous reports showed that the Rh2 epimers demonstrated different pharmacological activities and only (20S)-ginsenoside Rh2 showed potent proliferation inhibition on cancer cells in vitro. However, the in vivo anti-hepatoma activity of (20R)-ginsenoside Rh2 and (20S)-ginsenoside Rh2 has not been reported yet. This work assessed and compared the anti-hepatoma activities of (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 using H22 a hepatoma-bearing mouse model in vivo. In addition, hematoxylin and eosin staining, the deoxynucleotidyl transferase dUTP nick-end labeling assay, and the semiquantitative reverse transcriptase polymerase chain reaction method were used to further study the apoptosis of the tumors. The results showed that both (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 suppressed the growth of H22 transplanted tumors in vivo, and the highest inhibition rate could be up to 42.2 and 46.8 %, respectively (p < 0.05). Further, hematoxylin/eosin staining and the deoxynucleotidyl transferase dUTP nick-end labeling assay indicated that both (20R)-ginsenoside Rh2 and (20S)-ginsenoside Rh2 could induce H22 hepatoma tumor cell apoptosis, with apoptosis indexes of 3.87 %, and 3.80 %, respectively (p < 0.05). Moreover, this effect was accompanied by downregulating the level of Bcl-2 mRNA. In conclusion, both (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 can suppress the growth of H22 hepatomas without causing severe side effects, and this effect is associated with the induction of apoptosis. PMID:27163230
Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity
Chen, Ronald JY; Chung, Tse-yu; Li, Feng-yin; Lin, Nan-hei; Tzen, Jason TC
Aim: To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Methods: The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginsenosides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. Results: Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibitory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 position of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these positions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. Conclusion: The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhibition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure. PMID:19060914
Integrated evaluation of malonyl ginsenosides, amino acids and polysaccharides in fresh and processed ginseng.
Wan, Jin-Yi; Fan, Yong; Yu, Qing-Tao; Ge, Ya-Zhong; Yan, Chen-Pu; Alolga, Raphael N; Li, Ping; Ma, Zhong-Hua; Qi, Lian-Wen
Many analytical methods have been developed to characterize ginsenosides in ginseng. Relatively less attention has been paid to the malonyl ginsenosides, amino acids and polysaccharides in various processing ginsengs. In this study, malonyl ginsenosides were characterized by LC-Q-TOF/MS. In positive mode, the most abundant ions at m/z 425.38 were observed corresponding to the protopanoxadiol-type ginsenosides. A rich diagnostic ion at 835.48 was shown representing the malonyl ginsenosides with at least two glucosides. Twelve malonyl ginsenosides were rapidly screened using 835.48-835.49 to restructure ion chromatograms. In negative mode, besides the high deprotonated ion, a neutral loss of 44 Da (CO2) was found. High-energy collision-induced dissociation at 50 V produced the most abundant product ion [M-H-malonyl](-) by a neutral loss of 86 Da. Determination of 17 common amino acids was performed on an automatic amino acid analyzer. Arginine, glutamic acid, and aspartic acid were abundant. The contents of amino acids were 9.1% in fresh ginseng and 3.1% in black ginseng. Phenol-sulfuric acid method was applied to analysis of polysaccharides. The contents of polysaccharides were 29.1% in fresh ginseng and 11.1% in black ginseng. The optimal growth age for the accumulation of constituents was supposed to be 5-6 years. In conclusion, the contents of malonyl ginsenosides, amino acids, and polysaccharides, based on decreasing order, ranked as follows: fresh ginseng>frozen ginseng>white ginseng>stoved ginseng>red ginseng>black ginseng. Processing should be paid more attention for the quality control of ginseng products. PMID:25575174
Identification and Characterization of a Ginsenoside-Transforming β-Glucosidase from Pseudonocardia sp. Gsoil 1536 and Its Application for Enhanced Production of Minor Ginsenoside Rg2(S)
Park, Sung Chul; Kim, Jin-Kwang; Yu, Hong-Shan; Jin, Feng-Xie; Sun, Changkai; Kim, Sun-Chang; Im, Wan-Taek
The ginsenoside Rg2(S), which is one of the pharmaceutical components of ginseng, is known to have neuroprotective, anti-inflammation, and anti-diabetic effects. However, the usage of ginsenoside Rg2(S) is restricted owing to the small amounts found in white and red ginseng. To enhance the production of ginsenoside Rg2(S) as a 100 gram unit with high specificity, yield, and purity, an enzymatic bioconversion method was developed to adopt the recombinant glycoside hydrolase (BglPC28), which is a ginsenoside-transforming recombinant β-glucosidase from Pseudonocardia sp. strain Gsoil 1536. The gene, termed bglPC28, encoding β-glucosidase (BglPC28) belonging to the glycoside hydrolase family 3 was cloned. bglPC28 consists of 2,232 bp (743 amino acid residues) with a predicted molecular mass of 78,975 Da. This enzyme was overexpressed in Escherichia coli BL21(DE3) using a GST-fused pGEX 4T-1 vector system. The optimum conditions of the recombinant BglPC28 were pH 7.0 and 37°C. BglPC28 can effectively transform the ginsenoside Re to Rg2(S); the Km values of PNPG and Re were 6.36±1.10 and 1.42±0.13 mM, respectively, and the Vmax values were 40.0±2.55 and 5.62±0.21 µmol min−1 mg−1 of protein, respectively. A scaled-up biotransformation reaction was performed in a 10 L jar fermenter at pH 7.0 and 30°C for 12 hours with a concentration of 20 mg/ml of ginsenoside Re from American ginseng roots. Finally, 113 g of Rg2(S) was produced from 150 g of Re with 84.0±1.1% chromatographic purity. These results suggest that this enzymatic method could be usefully exploited in the preparation of ginsenoside Rg2(S) in the cosmetics, functional food, and pharmaceutical industries. PMID:24911166
Structure–inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs)
Fang, Zhong-Ze; Cao, Yun-Feng; Hu, Cui-Min; Hong, Mo; Sun, Xiao-Yu; Ge, Guang-Bo; Liu, Yong; Zhang, Yan-Yan; Yang, Ling; Sun, Hong-Zhi
The wide utilization of ginseng provides the high risk of herb–drug interaction (HDI) with many clinical drugs. The inhibition of ginsenosides towards drug-metabolizing enzymes (DMEs) has been regarded as an important reason for herb–drug interaction (HDI). Compared with the deep studies on the ginsenosides' inhibition towards cytochrome P450 (CYP), the inhibition of ginsenosides towards the important phase II enzymes UDP-glucuronosyltransferases (UGTs) remains to be unclear. The present study aims to evaluate the inhibition behavior of ginsenosides towards important UGT isoforms located in the liver and intestine using in vitro methods. The recombinant UGT isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as in vitro probe reaction. The results showed that structure-dependent inhibition existed for the inhibition of ginsenosides towards UGT isoforms. To clarify the possibility of in vivo herb–drug interaction induced by this kind of inhibition, the ginsenoside Rg{sub 3} was selected as an example, and the inhibition kinetic type and parameters (K{sub i}) were determined. Rg{sub 3} competitively inhibited UGT1A7, 2B7 and 2B15-catalyzed 4-MU glucuronidation reaction, and exerted noncompetitive inhibition towards UGT1A8-catalyzed 4-MU glucuronidation. The inhibition parameters (K{sub i} values) were calculated to be 22.6, 7.9, 1.9, and 2.0 μM for UGT1A7, 1A8, 2B7 and 2B15. Using human maximum plasma concentration of Rg{sub 3} (400 ng/ml (0.5 μM)) after intramuscular injection of 60 mg Rg{sub 3}, the area under the plasma concentration-time curve (AUC) was extrapolated to increase by 2.2%, 6.3%, 26.3%, and 25% for the co-administered drugs completely undergoing the metabolism catalyzed by UGT1A7, 1A8, 2B7 and 2B15, respectively. All these results indicated that the ginsenosides' inhibition towards UGT isoforms might be an important reason for ginseng–drug interaction. - Highlights: ► Structure-dependent inhibition of
Quality Characteristics and Ginsenosides Composition of Ginseng-Yakju According to the Particle Size of Ginseng Powder
Lee, Je-Hyuk; Choi, Kang Hyun; Sohn, Eun-Hwa; Jang, Ki-Hyo
The aim of this study was to develop rice wine (Yakju) containing various amounts and particle sizes of ginseng powder and to analyze the physicochemical characteristics and content of ginsenosides in ginseng-Yakju. Soluble solid content, pH, ethanol concentration, acidity, amino acid content, and evaluation of preference showed no difference between four kinds of Yakju groups, regardless of ginseng supplementation and particle size of the ginseng powder. During fermentation of Yakju containing ginseng, the contents of ginsenosides Rb1, Rb2, Rb3, and Rc were decreased. Otherwise, the content of ginsenoside Rh1 was increased highly by brewing microorganisms in Yakju. Recovery ratios of ginsenosides in ginseng-Yakju were approximately 25.4% (coarse ginseng power) and 23.8% (fine ginseng powder), which were superior to the recovery ratio of ginsenosides in Yakju containing ginseng slices (5%). PMID:24551824
Enhancing Biosynthesis of a Ginsenoside Precursor by Self-Assembly of Two Key Enzymes in Pichia pastoris.
Zhao, Chengcheng; Gao, Xin; Liu, Xinbin; Wang, Yong; Yang, Shengli; Wang, Fengqing; Ren, Yuhong
Ginsenosides from the edible and medicinal plant ginseng have demonstrated various pharmacological activities. However, producing ginsenoside efficiently remains a challenge. Engineering metabolic pathways through protein assembly in yeast is a promising way for ginsenoside production. In the biosynthetic pathway of ginsenosides, dammarenediol-II synthase and squalene epoxidase are two key enzymes that determine the production rate of the dammarane-type ginsenoside precursor dammarenediol-II. In this work, a strategy to enhance the biosynthesis of dammarenediol-II in Pichia pastoris was developed by the self-assembly of the two key enzymes via protein-protein interaction. After being modified by interacting proteins, the two enzymes were successfully co-localized, resulting in a 2.1-fold enhancement in dammarenediol-II yields. PMID:27074597
Biochemical basis of cancer chemoprevention and/or chemotherapy with ginsenosides (Review).
Choi, Joon-Seok; Chun, Kyung-Soo; Kundu, Juthika; Kundu, Joydeb Kumar
Cancer still imposes a global threat to public health. After decades of research on cancer biology and enormous efforts in developing anticancer therapies, we now understand that the majority of cancers can be prevented. Bioactive phytochemicals present in edible plants have been shown to reduce the risk of various types of cancer. Ginseng (Panax ginseng C.A. Meyer), which contains a wide variety of saponins, known as ginsenosides, is an age-old remedy for human ailments, including cancer. Numerous laboratory-based studies have revealed the anticancer properties of ginsenosides, which compel tumor cells to commit suicide, arrest the proliferation of cancer cells in culture and inhibit experimentally-induced tumor formation in laboratory animals. Ginsenosides have been reported to inhibit tumor angiogenesis, as well as the invasion and metastasis of various types of cancer cells. Moreover, ginsenosides as combination therapy enhance the sensitivity of chemoresistant tumors to clinically used chemotherapeutic agents. This review sheds light on the molecular mechanisms underlying the cancer chemopreventive and/or chemotherapeutic activity of ginsenosides and their intestinal metabolites with particular focus on the modulation of cell signaling pathways associated with oxidative stress, inflammation, cell proliferation, apoptosis, angiogenesis and the metastasis of cancer cells. PMID:24126942
The melanogenesis-inhibitory effect and the percutaneous formulation of ginsenoside Rb1.
Wang, Lin; Lu, Ai-Ping; Yu, Zhi-Ling; Wong, Ricky N S; Bian, Zhao-Xiang; Kwok, Hoi-Hin; Yue, Patrick Ying-Kit; Zhou, Li-Min; Chen, HuBiao; Xu, Min; Yang, Zhijun
Ginsenoside Rb1 (Rb1) is the most predominant ginsenoside isolated from the roots of ginseng (Panax ginseng C. A. Meyer). This compound is active in various human biological pathways that are involved in human collagen synthesis and inhibition of cell apoptosis. In this study, the skin-whitening effects of Rb1 were investigated in B16 melanoma cells. Our results showed that Rb1 inhibited melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 cells in a dose-dependent manner, which collectively indicated that Rb1 may have skin-whitening effects and may be formulated into skin-whitening products for skin care. Accordingly, a ginsenoside collagen transdermal patch was developed as a vehicle to topically deliver Rb1 into pig skin. The percutaneous permeation, retention within skin, and release in vitro of Rb1 from seven transdermal patch formulas were studied. It was determined that the best formula for ginsenoside collagen transdermal patch is made of protein collagen hydrolysate powder (PCHP) 2.0% (w/w), methyl cellulose (MC) 0.5% (w/w), polyethyleneglycol 6000 (PEG6000) 0.5% (w/w), ginsenoside 0.036% (w/w), azone 0.4% (v/w), menthol 0.20% (w/w), and water. PMID:24895076
Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea
Upadhyaya, Jitendra; Kim, Min-Ji; Kim, Young-Hoi; Ko, Sung-Ryong; Park, Hee-Won; Kim, Myung-Kon
Background Minor saponins or human intestinal bacterial metabolites, such as ginsenosides Rg3, F2, Rh2, and compound K, are more pharmacologically active than major saponins, such as ginsenosides Rb1, Rb2, and Rc. In this work, enzymatic hydrolysis of ginsenoside Rb1 was studied using enzyme preparations from cultured mycelia of mushrooms. Methods Mycelia of Armillaria mellea, Ganoderma lucidum, Phellinus linteus, Elfvingia applanata, and Pleurotus ostreatus were cultivated in liquid media at 25°C for 2 wk. Enzyme preparations from cultured mycelia of five mushrooms were obtained by mycelia separation from cultured broth, enzyme extraction, ammonium sulfate (30–80%) precipitation, dialysis, and freeze drying, respectively. The enzyme preparations were used for enzymatic hydrolysis of ginsenoside Rb1. Results Among the mushrooms used in this study, the enzyme preparation from cultured mycelia of A. mellea (AMMEP) was found to convert ginsenoside Rb1 into compound K with a high yield, while those from G. lucidum, P. linteus, E. applanata, and P. ostreatus produced remarkable amounts of ginsenoside Rd from ginsenoside Rb1. The enzymatic hydrolysis pathway of ginsenoside Rb1 by AMMEP was Rb1 → Rd → F2 → compound K. The optimum reaction conditions for compound K formation from ginsenoside Rb1 were as follows: reaction time 72–96 h, pH 4.0–4.5, and temperature 45–55°C. Conclusion AMMEP can be used to produce the human intestinal bacterial metabolite, compound K, from ginsenoside Rb1 with a high yield and without food safety issues. PMID:27158230
The effects of dynamic changes of malonyl ginsenosides on evaluation and quality control of Panax ginseng C.A. Meyer.
Liu, Zhi; Li, Yu; Li, Xiang; Ruan, Chang-Chun; Wang, Li-Juan; Sun, Guang-Zhi
To clarify the effects of malonyl ginsenosides (MGR) on evaluation and quality control of Panax ginseng, the contents of neutral and malonyl ginsenosides from P. ginseng were examined by high-performance liquid chromatography equipped with UV-VIS detector (HPLC-UV) during extraction, processing and storage. Several solvents, including water, ethanol, methanol, and n-butanol were used in the cold-soaked extraction (CSE). Among the four extraction solvents, methanol was found to be the most efficient. CSE was compared with other extraction methods such as Soxhlet extraction (SE), heat reflux extraction (HRE), ultrasonic-assisted extraction (UAE), and microwave-assisted extraction (MAE). The content of MGR showed significant differences, higher in CSE and UAE; lower in MAE and HRE; no MGR could be detected after SE. However, the total contents of neutral and malonyl ginsenosides were not different. Meanwhile, white ginseng, stored at 25°C in air of low humidity, showed a marked decrease in the concentration of MGR from 1.19% to 0.63% but with an increase in the neutral ginsenosides from 1.12% to 1.53% after 0-9-month storage. The results indicated that MGR changed dynamically in P. ginseng with different extraction solvents, extraction methods and increasing storage time. The total ginsenosides was not only underestimated but also determined imprecisely by ignoring malonyl ginsenosides. On the basis of our results, we suggest that malonyl ginsenosides should be transformed into the corresponding neutral ginsenosides during sample preparation for quality control and evaluation of P. ginseng. Then the content of six neutral ginsenosides in samples was used as the true level of total ginsenosides. The results reported here might provide useful information for accurate evaluation and quality control of P. ginseng. PMID:22387101
Isolation and determination of ginsenosides in American ginseng leaves and root extracts by LC-MS.
Ligor, T; Ludwiczuk, A; Wolski, T; Buszewski, B
Ginseng saponins (ginsenosides) were extracted from the root and leaves of locally cultivated American ginseng (Panax quinquefolium L.). For the isolation of compounds from plant samples three different extraction methods were utilized: accelerated solvent extraction, the ultrasound-assisted solvent extraction and mechanical shaking assisted solvent extraction. The separation of compounds was achieved with a water-acetonitrile gradient system using a C18 reversed-phase column. Target compounds were identified in MS(2) and MS(3) experiments. The relative distribution of these ginsenosides in each root and leaf extract was established. The limit of detection of the method was less than 30 ng/ml. Recovery of ginseng saponins in spiked samples exceeded 80%, while the relative standard deviation ranged from 7.1 to 9.1%. The total concentrations of ginsenosides were 41 and 13 mg/g in root and leaves. PMID:16283269
Ginsenoside extraction from Panax quinquefolium L. (American ginseng) root by using ultrahigh pressure.
Zhang, Shouqin; Chen, Ruizhan; Wu, Hua; Wang, Changzheng
A new method of ultrahigh pressure extraction (UPE) was used to extract the ginsenosides from Panax quinquefolium L. (American ginseng) root at room temperature. Several solvents, including water, ethanol, methanol, and n-butanol were used in the UPE. The ginsenosides were quantified by a HPLC equipped with UV-vis detector. The results showed that ethanol is the most efficient solvent among the used ones. Compared with other methods, i.e., Soxhlet extraction, heat reflux extraction, ultrasound-assisted extraction, microwave-assisted extraction, and supercritical CO2 extraction, the UPE has the highest extraction yield in the shortest time. The extraction yield of 0.861% ginsenoside-Rc in 2 min was achieved by the UPE, while the yields of 0.284% and 0.661% were obtained in several hours by supercritical CO2 extraction and the heat reflux extraction, respectively. PMID:16332422
Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer binding proteins and cyclic AMP response binding protein
Jeong, Hye Gwang; Pokharel, Yuba Raj; Han, Eun Hee; Kang, Keon Wook . E-mail: firstname.lastname@example.com
Panax ginseng is a widely used herbal medicine in East Asia and is reported to have a variety of pharmacological effects against cardiovascular diseases and cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. Rd (100 {mu}g/ml), but not other ginsenosides induced COX-2 and increased prostaglandin E{sub 2} production. Gel shift and Western blot analyses using nuclear fractions revealed that Rd increased both the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein (C/EBP){alpha}/{beta} and cyclic AMP response element binding protein (CREB), but not of p65, in RAW264.7 cells. Moreover, Rd increased the luciferase reporter gene activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site-specific mutation analyses confirmed that Rd-mediated transcriptional activation of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB appears to be essential for induction of COX-2 in RAW264.7 cells.
Morphological and Ginsenoside Differences among North American Ginseng Leaves
Proctor, John T. A.; Sullivan, Alan J.; Rupasinghe, Vasantha P. V.; Jackson, Chung-Ja C.
Leaf characteristics of mature 2, 3 and 4-year-old North American ginseng (Panax quinquefolius L.) leaves on fruiting and non-fruiting (NF) plants were studied. Leaflets of the 2-year-old plants had the lowest fresh and dry weight, area, volume and internal gas volume. Inflorescence removal in 3-year-old plants did not affect leaf characteristics or ginsenoside concentration but in 4-yearold plants it increased leaf fresh (38.6%) and dry (43.9%) weight, leaf area (29.1%), specific leaf mass (11.4%), leaf volume (43.1%), and leaf thickness (12.1%), and decreased leaf water content (6.2%). Cultivated ginseng, although an understorey plant, had the specific leaf mass, 35.6 g m-2 (range, 36 to 39 g m-2) and a chlorophyll a/b ratio of 2.40 to 2.61, both suggesting the ability to perform like a sunny habitat plant. Also, specific leaf mass of 35.6 g m-2 is similar to that reported for perennial plants, 36.8 g m-2, rather than that for annuals, 30.9 g m-2. PMID:23717057
Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice.
Yang, Zhigang; Chen, Aqin; Sun, Hongxiang; Ye, Yiping; Fang, Weihuan
Ginsenoside Rd (Rd), a saponin isolated from the roots of panax notoginseng, was evaluated for inducing Th1 or Th2 immune responses in mice against ovalbumin (OVA). ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing alum (200 microg), or Rd (10, 25 or 50 microg) on days 1 and 15. Two weeks later (day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation was determined using MTT assay, and OVA-specific antibody titers and levels of cytokines in serum were measured by ELISA and microparticle-based flow cytometric immunoassay, as well as peripheral blood T-lymphocyte subsets analyzed using flow cytometer. Rd significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice. OVA-specific IgG, IgG1, and IgG2b antibody titers in serum were significantly enhanced by Rd compared with OVA control group. Meanwhile, Rd also significantly promoted the production of the Th1 and Th2 cytokines in OVA-immunized mice. Further, the effects of Rd on expression of cytokine mRNA in Con A-stimulated mice splenocytes were evaluated by RT-PCR analysis. Rd significantly enhanced the interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, and IL-10 mRNA expression in mice splenocyte induced by Con A. These results suggested that Rd had immunological adjuvant activity, and elicited a Th1 and Th2 immune response by regulating production and gene expression of Th1 cytokines and Th2 cytokines. PMID:16950547
Effects of Total Ginsenosides on the Feeding Behavior and Two Enzymes Activities of Mythimna separata (Walker) Larvae.
Zhang, Ai-Hua; Tan, Shi-Qiang; Zhao, Yan; Lei, Feng-Jie; Zhang, Lian-Xue
Ginsenosides, the main effective components of Panax ginseng C.A. Meyer and Panax quinquefolius L., are important allelochemicals of ginseng. Although many studies have targeted the pharmacological, chemical, and clinical properties of ginsenosides, little is known about their ecological role in ginseng population adaptation and evolution. Pests rarely feed on ginseng, and it is not known why. This study investigated the effects of total ginsenosides on feeding behavior and activities of acetylcholinesterase (AChE) and glutathione s-transferase (GST) in Mythimna separata (Walker) larvae. The results showed that the total ginsenosides had significant antifeeding activity against M. separata larvae, determined by nonselective and selective antifeeding bioassays. In addition, the total ginsenosides had inhibitory effects on the activities of GST and AChE. The antifeeding ratio was the highest at 8 h, then decreased, and was the lowest at 16 h. Both GST and AChE activities decreased from 0 h to 48 h in all total ginsenosides treatments but increased at 72 h. Total ginsenosides had antifeeding activity against M. separata larvae and inhibitory effects on the activities of GST and AChE. PMID:26074991
Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2
Zhang, Hui; Gong, Jian; Zhang, Huilai; Kong, Di
Multidrug resistance is a phenomenon that cancer cells develop a cross-resistant phenotype against several unrelated drugs, and permeability glycoprotein derived from the overexpression of multidrug resistance gene 1 has been taken as the most significant cause of multidrug resistance. In the present study, ginsenoside Rh2 was used to reverse permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM cell line. Effects of ginsenoside Rh2 on the apoptotic process and caspase-3 activity of MCF-7 and MCF-7/ADM cell lines were determined using flow cytometry and microplate reader. Methyl thiazolyl tetrazolium test was conducted to assess the IC50 values of ginsenoside Rh2 and adriamycin on MCF-7 and MCF-7/ADM cultures; Rhodamin 123 assay was used to assess the retention of permeability glycoprotein after ginsenoside Rh2 treatment; flow cytometry and real time polymerase chain reaction were used to determine the expression levels of permeability glycoprotein and multidrug resistance gene 1 in drug-resistant cells and their parental cells after exposure to ginsenoside Rh2. The results showed that ginsenoside Rh2, except for inducing apoptosis, had the ability to reverse multidrug resistance in MCF-7/ADM cell line without changing the expression levels of permeability glycoprotein and multidrug resistance gene 1. Our findings provided some valuable information for the application of ginsenoside Rh2 in cancer therapy, especially for multidrug resistance reversal in clinic. PMID:26191135
Ginsenosides may enhance the functionality of human embryonic stem cell-derived cardiomyocytes in vitro.
Kim, Yoon Young; Ku, Jun Beom; Liu, Hung Ching; Ku, Seung-Yup; Kim, Seok Hyun; Choi, Young Min
Various chemicals have been reported to induce the differentiation of human embryonic stem cells (hESCs) into cardiomyocytes (CMs), however, their contributions to the functionality of hESC-derived CMs are still limited. In this study, we evaluated the effects of red ginseng extract (RGE), ginsenoside-Rb1 (gRb1, panaxadiol), and ginsenoside-Re (gRe, panaxatriol) on the differentiation of hESCs and the functionality of derived CMs. Undifferentiated hESCs were treated with 0.25 mg/mL RGE, 10 μmol/L gRb1, or 10 μmol/L gRe for 48 hours at the differentiation induction (early stage) or maturation (late stage) period. The expression of mesodermal and cardiac transcription factor genes was upregulated in the ginsenoside-treated groups from early stage. The expression of cardiac sarcomeric genes was significantly upregulated at the late stage. The gRb1- and gRe-treated groups upregulated the expression of potassium voltage-gated channel subfamily E member 1 (KCNE1) and the gRe-treated group showed a longer beating duration compared to the control. Taken together, ginsenosides may enhance the functionality of hESC-derived CMs in vitro. PMID:24615935
Large Scale Culture of Ginseng Adventitious Roots for Production of Ginsenosides
NASA Astrophysics Data System (ADS)
Paek, Kee-Yoeup; Murthy, Hosakatte Niranjana; Hahn, Eun-Joo; Zhong, Jian-Jiang
Ginseng (Panax ginseng C. A. Meyer) is one of the most famous oriental medicinal plants used as crude drugs in Asian countries, and now it is being used worldwide for preventive and therapeutic purposes. Among diverse constituents of ginseng, saponins (ginsenosides) have been found to be major components responsible for their biological and pharmacological actions. On the other hand, difficulties in the supply of pure ginsenosides in quantity prevent the development of ginseng for clinical medicines. Cultivation of ginseng in fields takes a long time, generally 5-7 years, and needs extensive effort regarding quality control since growth is susceptible to many environmental factors including soil, shade, climate, pathogens and pests. To solve the problems, cell and tissue cultures have been widely explored for more rapid and efficient production of ginseng biomass and ginsenosides. Recently, cell and adventitious root cultures of P. ginseng have been established in large scale bioreactors with a view to commercial application. Various physiological and engineering parameters affecting the biomass production and ginsenoside accumulation have been investigated. Advances in adventitious root cultures including factors for process scale-up are reviewed in this chapter. In addition, biosafety analyses of ginseng adventitious roots are also discussed for real application.
Ginsenoside Re Attenuates Neuroinflammation in a Symptomatic ALS Animal Model.
Cai, Mudan; Yang, Eun Jin
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, which cause paralysis and respiratory dysfunction. There is currently no permanently effective drug for patients with ALS. Ginsenoside Re (G-Re), one of the most active ingredients of ginseng, has pharmacological activities that affect a number of targets. To investigate the effects of G-Re on neuroinflammation, we used G-Re (2.5[Formula: see text][Formula: see text]g/g) at the Joksamni acupressure point (ST36) once every other day for one week. To evaluate G-Re function in symptomatic human-superoxide dismutase 1 (hSOD1[Formula: see text] transgenic mice, immunohistochemistry and Western blot analysis were performed with the spinal cord of symptomatic hSOD1(G93A) transgenic mice. Here, we report that G-Re exhibits potent neuroprotective effects against neuroinflammation in a murine model of ALS. G-Re treatment reduced the loss of motor neurons and active-microglia-related expression of Iba-1 in the spinal cord of symptomatic hSOD1(G93A) transgenic mice. In addition, compared with age-matched hSOD1(G93A) mice, G-Re-treated hSOD1(G93A) mice showed a significant reduction in expression of pro-inflammatory proteins such as CD14 and TNF-[Formula: see text] protein related to TLR4 signaling pathway. G-Re administration also led to a decrease in cell death-related phospho-p38 protein levels, and had an antioxidative effect by reducing HO1 expression. Together, our data suggest that G-Re could have potent anti-neuroinflammatory effects on ALS by inhibiting the TLR4 pathway. PMID:27080948
Neuroprotective Effect of Ginsenoside Rd in Spinal Cord Injury Rats.
Cong, Lin; Chen, Wenting
In this study, the neuroprotective effects of ginsenoside Rd (GS Rd) were evaluated in a rat model of spinal cord injury (SCI). Rats in SCI groups received a T8 laminectomy and a spinal contusion injury. GS Rd 12.5, 25 and 50 mg/kg were administered intraperitoneally 1 hr before the surgery and once daily for 14 days. Dexamethasone 1 mg/kg was administered as a positive control. Locomotor function was evaluated using the BBB score system. H&E staining and Nissl staining were performed to observe the histological changes in the spinal cord. The levels of MDA and GSH and the activity of SOD were assessed to reflect the oxidative stress state. The production of TNF-α, IL-1β and IL-1 was assessed using ELISA kits to examine the inflammatory responses in the spinal cord. TUNEL staining was used to detect the cell apoptosis in the spinal cord. Western blot analysis was used to examine the expression of apoptosis-associated proteins and MAPK proteins. The results demonstrated that GS Rd 25 and 50 mg/kg significantly improved the locomotor function of rats after SCI, reduced tissue injury and increased neuron survival in the spinal cord. Mechanically, GS Rd decreased MDA level, increased GSH level and SOD activity, reduced the production of pro-inflammatory cytokines and prevented cell apoptosis. The effects were equivalent to those of dexamethasone. In addition, GS Rd effectively inhibited the activation of MAPK signalling pathway induced by SCI, which might be involved in the protective effects of GS Rd against SCI. In conclusion, GS Rd attenuates SCI-induced secondary injury through reversing the redox-state imbalance, inhibiting the inflammatory response and apoptosis in the spinal cord tissue. PMID:26833867
The antitumor activity study of ginsenosides and metabolites in lung cancer cell
Xu, Feng-Yuan; Shang, Wen-Qing; Yu, Jia-Jun; Sun, Qian; Li, Ming-Qing; Sun, Jian-Song
Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and antitumor activity. Ginsenosides are the main biological components of ginseng. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides. However, the difference between these compounds in anti-lung cancer is unclear. The present study aimed to evaluate the antitumor activity of PPD, PPT, Ginsenosides-Rg3 (G-Rg3) and Ginsenosides-Rh2 (G-Rh2) in lung cancer cell. After treatment with cisplatin, PPD, PPT, G-Rg3 or G-Rh2, the viability, apoptosis level and invasiveness of lung cell lines (A549 cell, a lung adenocarcinoma cell line and SK-MES-1 cell, a lung squamous cell line) in vitro were analyzed by Cell Counting Kit-8 (CCK8), Annexin V/PI apoptosis and Matrigel invasion assays, respectively. Here we found that all these compounds led to significant decreases of viability and invasiveness and an obvious increase of apoptosis of A549 and SK-MES-1 cells. Among these, the viability of SK-MES-1 cell treated with PPT was decreased to 66.8%, and this effect was closest to Cisplatin. G-Rg3 had the highest stimulatory effect on apoptosis, and PTT had the highest inhibitory effect on cell invasiveness in A549 and SK-MES-1 cells. These results indicate that both ginsenosides and two metabolites have antitumor activity on lung cancer cell in vitro. However, PPT is more powerful for inhibiting the viability and invasiveness of lung cancer cell, especially lung squamous cell. G-Rg3 has the best pro-apoptosis effects. This study provides a scientific basis for potential therapeutic strategies targeted to lung cancer by further structure modification. PMID:27186294
Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Weifuchun tablet.
Jin, Yiran; Tian, Tingting; Ma, Yinghua; Xu, Huijun; Du, Yingfeng
A sensitive, specific and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma using sulfamethoxazole as an internal standard (IS). Separation was conducted out on an Agilent Eclipse XDB C18 column with liner gradient elution using acetonitrile (A) and 0.1% aqueous acetic acid (B). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting three scanning periods. All analytes exhibited good linearity within the concentration range (r>0.9973). The lower limits of quantitation (LLOQ) of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin were 2.64, 4.32, 2.32 and 1.56ng/mL, respectively. Intra-day and inter-day precisions of the investigated components exhibited an RSD within 8.3%, and the accuracy (RE) ranged from -8.6% to 6.0% at all quality control levels. The developed method was successfully applied to a pharmacokinetic study of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rats after oral administration of a Weifuchun tablet. PMID:26222904
Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway.
Kim, Wang-Kyun; Song, Seung-Yong; Oh, Won Keun; Kaewsuwan, Sireewan; Tran, Tien Lam; Kim, Won-Serk; Sung, Jong-Hyuk
Panax ginseng is considered as one of the most valuable medicinal herbs in traditional medicine, and ginsenoside Rd is one of the main active ingredients in P. ginseng leaf. Although there is significant number of evidences implicated on the beneficial effects of the ginsenosides with diverse associated mechanisms, reports on the skin regeneration by the ginsenoside Rd are not sufficient. Therefore, we examined the mitogenic and protective effects of the ginsenoside Rd in the keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (HDFs). Furthermore, the signaling pathways involved in the activation of KPCs and HDFs were investigated, and wound-healing effect is evaluated in vivo through animal wound models. We found that the ginsenoside Rd significantly increased the proliferation and migration level of KPCs and HDFs in a dose-dependent manner. Additionally, the cell survival was significantly increased in H2O2 treated KPCs. Moreover, the ginsenoside Rd effectively induced collagen type 1 and down-regulated matrix metalloprotinase-1 (MMP-1) in a dose-dependent manner. All of these beneficial effects are associated with an induction of intracellular cAMP levels and phosphorylated cAMP response element-binding protein expression in nucleus, which both attenuated by adenine 9-β-d-arabinofuranoside, an adenylate cyclase inhibitor. Application of the ginsenoside Rd to an excision wound in mice showed an effective healing process. As skin regeneration is mainly associated with the activation of HDFs and KPCs, P. ginseng leaf, an alternative source of the ginsenoside Rd, can be used as a natural source for skin regeneration. PMID:23399764
Enzymatic transformation of ginsenosides in Korean Red Ginseng (Panax ginseng Meyer) extract prepared by Spezyme and Optidex
Choi, Hyeon-Son; Kim, Sun Young; Park, Yooheon; Jung, Eun Young; Suh, Hyung Joo
Background In this study, we examined the effects of various enzymes on chemical conversions of ginsenosides in ginseng extract prepared by amylases. Methods Rapidase, Econase CE, Viscozyme, Ultraflo L, and Cytolase PCL5 were used for secondary enzymatic hydrolysis after amylase treatment of ginseng extract, and ginsenoside contents, skin permeability, and chemical compositions including total sugar, acidic polysaccharide, and polyphenols were determined on the hydrolyzed ginseng extract. Results Rapidase treatment significantly elevated total ginsenoside contents compared with the control (p < 0.05). In particular, deglycosylated ginsenosides including Rg3, which are known as bioactive compounds, were significantly increased after Rapidase treatment (p < 0.05). The Rapidase-treated group also increased the skin permeability of polyphenols compared with the control, showing the highest level of total sugar content among the enzyme treatment groups. Conclusion This result showed that Rapidase induced the conversion of ginsenoside glycosides to aglycones. Meanwhile, Cytolase PCL5 and Econase treatments led to a significant increase of uronic acid (acidic polysaccharide) level. Taken together, our data showed that the treatments of enzymes including Rapidase are useful for the conversion and increase of ginsenosides in ginseng extracts or products. PMID:25379006
Skin anti-photoaging properties of ginsenoside Rh2 epimers in UV-B-irradiated human keratinocyte cells.
Oh, Sun-Joo; Lee, Sihyeong; Choi, Woo-Yong; Lim, Chang-Jin
Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20(S)-ginsenoside Rh2 [20(S)-Rh2] and 20(R)-ginsenoside Rh2 [20(R)-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20(S)-Rh2 and 20(R)-Rh2 in UV-B-irradiated HaCat cells. 20(S)-Rh2, but not 20(R)-Rh2, was able to suppress UV-B-induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20(S)-Rh2 and 20(R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20(S)-Rh2 and 20(R)-Rh2, possess skin anti-photoaging effects but possibly in different fashions. PMID:25116621
Ginsenoside rb1 modulates level of monoamine neurotransmitters in mice frontal cortex and cerebellum in response to immobilization stress.
Lee, Sang Hee; Hur, Jinyoung; Lee, Eunjoo H; Kim, Sun Yeou
Cerebral monoamines play important roles as neurotransmitters that are associated with various stressful stimuli. Some components such as ginsenosides (triterpenoidal glycosides derived from the Ginseng Radix) may interact with monoamine systems. The aim of this study was to determine whether ginsenoside Rb1 can modulate levels of the monoamines such as dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), epinephrine (EP), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydorxytryptamine (5-HT), 5-hydroxindole-3-acetic acid (5-HIAA), and 5-hydroxytryptophan (5-HTP) in mice frontal cortex and cerebellum in response to immobilization stress. Mice were treated with ginsenoside Rb1 (10 mg/kg, oral) before a single 30 min immobilization stress. Acute immobilization stress resulted in elevation of monoamine levels in frontal cortex and cerebellum. Pretreatment with ginsenoside Rb1 attenuated the stress-induced changes in the levels of monoamines in each region. The present findings showed the anti-stress potential of ginsenoside Rb1 in relation to regulation effects on the cerebral monoaminergic systems. Therefore, the ginsenoside Rb1 may be a useful candidate for treating several brain symptoms related with stress. PMID:24009838
Microbial conversion of ginsenoside Rd from Rb1 by the fungus mutant Aspergillus niger strain TH-10a.
Feng, Li; Xu, Chunchun; Li, Zhuo; Li, Jing; Dai, Yulin; Han, Hongxiang; Yu, Shanshan; Liu, Shuying
Ginsenoside Rd, one of the ginsenosides with significant pharmaceutical activities, is getting more and more attractions on its biotransformation. In this study, a novel fungus mutant, the Aspergillus niger strain TH-10a, which can efficiently convert ginsenoside Rd from Rb1, was obtained through screening survival library of LiCl and ultraviolet (UV) irradiation. The transformation product ginsenoside Rd, generated by removing the outer glucose residue from the position C20 of ginsenoside Rb1, was identified through high-performance liquid chromatography (HPLC) analysis. Factors for the microbial culture and biotransformation were investigated in terms of the carbon sources, the nitrogen sources, pH values, and temperatures. This showed that maximum mycelia growth could be obtained at 28°C and pH 6.0 with cellobiose and tryptone as the carbon source and the nitrogen source, respectively. The highest transformation rate (∼86%) has been achieved at 32°C and pH 5.0 with the feeding time of substrate 48 hr. Also, Aspergillus niger strain TH-10a could tolerate even 40 mg/mL ginseng root extract as substrate with 60% bioconversion rate after 72 hr of treatment at the optimal condition. Our results highlight a novel ginsenoside Rd transformation fungus and illuminate its potentially practical application in the pharmaceutical industries. PMID:25831478
Genomic expression profiling and bioinformatics analysis on diabetic nephrology with ginsenoside Rg3
Wang, Juan; Cui, Chunli; Fu, Li; Xiao, Zili; Xie, Nanzi; Liu, Yang; Yu, Lu; Wang, Haifeng; Luo, Bangzhen
Diabetic nephropathy (DN), a common diabetes-related complication, is the leading cause of progressive chronic kidney disease (CKD) and end-stage renal disease. Despite the rapid development in the treatment of DN, currently available therapies used in early DN cannot prevent progressive CKD. The exact pathogenic mechanisms and the molecular events underlying DN development remain unclear. Ginsenoside Rg3 is a herbal medicine with numerous pharmacological effects. To gain a greater understanding of the molecular mechanism and signaling pathway underlying the effect of ginsenoside Rg3 in DN therapy, an RNA sequencing approach was performed to screen differential gene expression in a rat model of DN treated with ginsenoside Rg3. A combined bioinformatics analysis was then conducted to obtain insights into the underlying molecular mechanisms of the disease development, in order to identify potential novel targets for the treatment of DN. Six Sprague-Dawley male rats were randomly divided into 3 groups: Normal control group, DN group and ginsenoside-Rg3 treatment group, with two rats in each group. RNA sequencing was adopted for transcriptome profiling of cells from the renal cortex of DN rat model. Differentially expressed genes were screened out. Cluster analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to analyze the differentially expressed genes. In total, 78 differentially expressed genes in the DN control group were identified when compared with the normal control group, of which 52 genes were upregulated and 26 genes were downregulated. Differential expression of 43 genes was observed in the ginsenoside-Rg3 treatment group when compared with the DN control group, consisting of 10 upregulated genes and 33 downregulated genes. Notably, 21 that were downregulated in the DN control group compared with the control were then shown to be upregulated in the ginsenoside-Rg3 treatment group compared with the DN
Simultaneous enantiomer determination of 20 (R)- and 20 (S)-ginsenoside-Rg2 in rat plasma after intravenous administration using HPLC method.
Gui, Fang-Jin; Yang, Xiu-Wei; Li, Long-Yun; Tian, Jian-Ming
20 (R,S)-Ginsenoside-Rg2, an anti-shock agent, is prescribed as a racemate. To analyze simultaneously the enantiomers of 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2 in plasma, a simple and reproducible high-performance liquid chromatographic (HPLC) method has been developed. The enantiomeric separation and determination were successfully achieved using a Diamonsil ODS C18 reversed-phase column (5 microm, 250 mm x 4.6 mm) with an RP18 (5 microm) guard column and a mobile phase of MeOH-aq. 4% H3PO4 (65:35, v/v, pH 5.1) with UV detection at 203 nm. Both enantiomers, 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2, were well separated at 14.5 min and 13.6 min, respectively. The linear ranges of the standard curves were 2.0-250 microg/ml. The intra- and inter-day precision (R.S.D.) were
Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS
Yoon, Sung-Jin; Park, Jun-Young; Choi, Song; Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo; Shim, Sungbo; Park, Young-Jun
Ginsenoside Rg3, a specific biological effector, is well-known as a major bioactive ingredient of Panax ginseng. However, its role in the inflammasome activation process remains unclear. In this report, we demonstrate that ginsenosides 20(R)-Rg3 and 20(S)-Rg3 are capable of suppressing both lethal endotoxic shock and the S-nitrosylation of the NLRP3 inflammasome by inhibiting nitric oxide (NO) production through the regulation of inducible nitric oxide synthase (iNOS) expression. In response to lipopolysaccharide (LPS), the reducing effect of 20(S)-Rg3 and 20(R)-Rg3 on nitric oxide led to an increase in the survival time of mice after lethal endotoxin-induced shock, and excess levels of NO inhibited IL-1β production via the S-nitrosylation of the NLRP3 inflammasome. In addition, ginsenosides 20(R)-Rg3 and 20(S)-Rg3 had suppressive effects on the LPS- or UV-irradiation-induced reactive oxygen species (ROS) levels in macrophage and HaCaT cells and thereby prevented apoptosis of spleen cells in mice. Altogether, these results demonstrate that ginsenoside 20(R)-Rg3 and 20(S)-Rg3, a naturally occurring compound, might act as a dual therapeutic regulator for the treatment of inflammatory and oxidative stress-related diseases. - Highlights: • Ginsenosides Rg3 inhibits NO production through the regulation of iNOS expression. • Ginsenosides Rg3 inhibits the S-nitrosylation of the NLRP3 inflammasome. • Ginsenosides Rg3 suppress on the LPS- or UV-irradiation-induced ROS levels in cells.
Stereoselective skin anti-photoaging properties of ginsenoside Rg3 in UV-B-irradiated keratinocytes.
Lim, Chang-Jin; Choi, Woo-Yong; Jung, Hyun-Joo
Ginsenosides are major bioactive constituents that are responsible for the diverse pharmacological activities of ginseng. This work aimed to assess the skin anti-photoaging activities of the two stereoisomeric forms of ginsenoside Rg3, 20(S)-Rg3 and 20(R)-Rg3. When the two Rg3 stereoisomers were added to cultured human keratinocyte HaCaT cells prior to irradiation with 70 mJ/cm(2) UV-B, 20(S)-Rg3, but not 20(R)-Rg3, decreased the UV-B-induced intracellular reactive oxygen species (ROS) levels in a concentration-dependent manner, as detected by both fluorometric and confocal microscopic analyses. Likewise, 20(S)-Rg3, but not 20(R)-Rg3, decreased the UV-B-induced ROS levels in human dermal fibroblast cells. Both stereoisomers were unable to modulate the nitric oxide levels in HaCaT cells under UV-B irradiation, and induced no cytotoxicity in cultured keratinocytes and fibroblasts. 20(S)-Rg3 suppressed the UV-B-induced matrix metalloproteinase (MMP)-2 activities in HaCaT cells. Taken together, these results indicate that 20(S)-Rg3 possesses both ROS-scavenging and MMP-2 inhibitory activities, while 20(R)-Rg3 possesses neither activity. These findings imply that ginsenoside Rg3 stereoselectively demonstrates skin anti-photoaging activities. PMID:25056231
Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts.
Wang, Pingping; Wei, Yongjun; Fan, Yun; Liu, Qunfang; Wei, Wei; Yang, Chengshuai; Zhang, Lei; Zhao, Guoping; Yue, Jianmin; Yan, Xing; Zhou, Zhihua
Ginsenosides Rh2 and Rg3 represent promising candidates for cancer prevention and therapy and have low toxicity. However, the concentrations of Rh2 and Rg3 are extremely low in the bioactive constituents (triterpene saponins) of ginseng. Despite the available heterologous biosynthesis of their aglycone (protopanaxadiol, PPD) in yeast, production of Rh2 and Rg3 by a synthetic biology approach was hindered by the absence of bioparts to glucosylate the C3 hydroxyl of PPD. In this study, two UDP-glycosyltransferases (UGTs) were cloned and identified from Panax ginseng. UGTPg45 selectively transfers a glucose moiety to the C3 hydroxyl of PPD and its ginsenosides. UGTPg29 selectively transfers a glucose moiety to the C3 glucose of Rh2 to form a 1-2-glycosidic bond. Based on the two UGTs and a yeast chassis to produce PPD, yeast cell factories were built to produce Rh2 and/or Rg3 from glucose. The turnover number (kcat) of UGTPg29 was more than 2500-fold that of UGTPg45, which might explain the higher Rg3 yield than that of Rh2 in the yeast cell factories. Building yeast cell factories to produce Rh2 or Rg3 from simple sugars by microbial fermentation provides an alternative approach to replace the traditional method of extracting ginsenosides from Panax plants. PMID:25769286
Improved production of ginsenosides in suspension cultures of ginseng by medium replenishment strategy.
Jeong, Cheol-Seung; Murthy, Hosakatte Niranjana; Hahn, Eun-Joo; Paek, Kee-Yoeup
The objective of this study was to improve the accumulation of ginsenosides by the adventitious root cultures of ginseng, which are important secondary metabolites with pharmaceutical applications. The adventitious roots were cultured in bioreactors for 50 d using 1.5-strength Murashige and Skoog (MS) medium supplemented with 10 mg/l indole acetic acid and 75 g/l sucrose. Kinetic studies of the nutrient composition of the spent medium revealed the gradual depletion of various inorganic nutrients and sugars. Cultures were supplied with fresh nutrient medium (medium exchange or replenishment with 0.75- and 1.0-strength MS medium) after 10 and 20 d of culture initiation to fulfill the nutritional requirements of adventitious roots. Medium replenishment strategy (with 1.0-strength MS medium after 20 d of culture) significantly improved the growth of adventitious roots and the biosynthesis of ginsenosides by the adventitious roots. This work is useful for the large-scale cultivation of adventitious roots for the production of ginsenosides. PMID:18397781
Effect of white, red and black ginseng on physicochemical properties and ginsenosides.
Jin, Yan; Kim, Yeon-Ju; Jeon, Ji-Na; Wang, Chao; Min, Jin-Woo; Noh, Hae-Yong; Yang, Deok-Chun
A systematic comparison of the ginsenosides and physicochemical properties of white ginseng (WG), red ginseng (RG) and black ginseng (BG) was performed. The purpose of the present study was to identify the effects of the physicochemical properties by steaming process. During the steaming process, ginsenosides transform into specific ginsenosides by hydrolysis, dehydration and isomerization at C-3, C-6 or C-20. Steaming ginseng led to a significant increase in reducing sugar, acidic polysaccharide and phenolic compounds content. Antioxidative properties were investigated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, compared with BHA (Butylated hydroxyanisole). RG and BG exhibited higher antioxidant activity than WG. The maximum residue level for Benzo(a)pyrene was established to 5 μg/kg in food products. The levels of benzo(a)pyrene in WG and RG were not detected. Benzo(a)pyrene was detected in the BG, the content was 0.17 μg/kg. The scientific achievements of the present study could help consumers to choose different type of ginseng products available on the market. PMID:25778283
Involvement of Connexin40 in the Protective Effects of Ginsenoside Rb1 Against Traumatic Brain Injury.
Chen, Wei; Guo, Yijun; Yang, Wenjin; Zheng, Ping; Zeng, Jinsong; Tong, Wusong
Ginsenosides are the major active components of ginseng, which have been proven to be effective in therapies for neurodegenerative diseases. Ginsenoside Rb1 (GS-Rb1) is the most abundant among all the identified ginsenosides and has been shown to exert neuroprotective effects, although the underlying molecular mechanisms remain unclear. Connexins are a family of transmembrane proteins that form gap junctions, which are important for diffusion of cytosolic factors such as ions and second messenger signaling molecules. Previous studies have shown that a subset of connexin proteins is involved in neuroprotection. We investigated the protective effects of GS-Rb1 against traumatic brain injury (TBI) and the potential mechanism using TBI mouse model. We discovered that TBI-induced brain injury and up-regulation of connexin40 (Cx40) protein expression as early as 6 h post-TBI, which was reversed by administration of GS-Rb1. In addition, we found that the protective effects of GS-Rb1 are dose and time dependent and are partially mediated through phosphorylation of ERK1/2 signaling pathway, as evidenced by the abolishment of GS-Rb1-mediated elevation of p-ERK1/2 expression and inhibition of Cx40 expressions when ERK inhibitor U0126 was used. Our study provides evidence that Cx40 is implicated in TBI-induced brain injuries, and GS-Rb1 exerts neuroprotective activity against TBI involving down-regulation of Cx40 expression. PMID:26645822
Whole-Cell Biocatalysis for Producing Ginsenoside Rd from Rb1 Using Lactobacillus rhamnosus GG.
Ku, Seockmo; You, Hyun Ju; Park, Myeong Soo; Ji, Geun Eog
Ginsenosides are the major active ingredients in ginseng used for human therapeutic plant medicines. One of the most well-known probiotic bacteria among the various strains on the functional food market is Lactobacillus rhamnosus GG. Biocatalytic methods using probiotic enzymes for producing deglycosylated ginsenosides such as Rd have a growing significance in the functional food industry. The addition of 2% cellobiose (w/v) to glucose-free de Man-Rogosa-Sharpe broths notably induced β-glucosidase production from L. rhamnosus GG. Enzyme production and activity were optimized at a pH, temperature, and cellobiose concentration of 6.0, 40°C, and 2% (w/v), respectively. Under these controlled conditions, β-glucosidase production in L. rhamnosus GG was enhanced by 25-fold. Additionally, whole-cell homogenates showed the highest β-glucosidase activity when compared with disrupted cell suspensions; the cell disruption step significantly decreased the β-glucosidase activity. Based on the optimized enzyme conditions, whole-cell L. rhamnosus GG was successfully used to convert ginsenoside Rb1 into Rd. PMID:27012233
Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}
Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung . E-mail: firstname.lastname@example.com
We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.
Isolation, Purification and Quantification of Ginsenoside F₅ and F₃ Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng.
Li, Ke-Ke; Xu, Fei; Gong, Xiao-Jie
In this paper, the isolation, purification and quantification of ginsenoside F₅ and F₃ isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at analytical scale was achieved using a Zorbax Eclipse XDB C-18 column with a ternary mobile phase of acetonitrile-water-phosphoric acid (28:71:1) at a flow rate of 1.0 mL/min within 40 min. UV detection was set at 203 nm. Ginsenoside F₅ and F₃ was 4.21 mg and 5.13 mg in 1 g flower buds of P. ginseng (FBPG), respectively. The preparation of ginsenoside F₅ and F₃ at semi-preparative scale was performed by using a Daisogel C-18 column and gradient elution system of acetonitrile-water (32:68 → 28:72) at a flow rate of 10 mL/min with a sample load of 20-30 mg, and yielded ginsenosides in purity of more than 96%. Their structures were characterized by NMR and high resolution electrospray ionization mass spectrometry (HRESIMS). All the method validations showed acceptable limits. The results indicate a new source to obtain ginsenoside F₅ and F₃, and show that the method developed here appears to be reliable for simultaneously preparing them from CEFBPG. PMID:27005606
Based on SERS conformational studies of ginsenoside Rb1 and its metabolites before and after combined with human serum albumin
NASA Astrophysics Data System (ADS)
Zhang, Wei; Wang, Yingping; Bai, Xueyuan; Zhao, Bing
Surface-enhanced Raman scattering (SERS) and fluorescence spectroscopy were employed to probe the interaction of the pharmaceutical and natural product molecules, ginsenoside Rb1, Rd, Rg3 and compound K (CK), with human serum albumin (HSA). Normal Raman spectra of these four ginsenosides were obtained from solid powder on glass slide. Based on the unsplit peak at 1445 cm-1, the stacking modes of ginsenoside Rb1, Rd, Rg3 and CK were quite similar, when the deconvolution of alkyl chain was not occurred. SERS spectra of ginsenoside Rb1, Rd, Rg3 and CK were obtained from a colloidal silver surface on a self-assembled SERS substrate, the most enhanced modes were those with certain motions perpendicular to the metal surface, such as C24dbnd C25 stretch and Csbnd H out-of-plane bending from alkyl chain. The SERS spectra were used to predict similar perpendicular orientation of flexible alkyl chain and parallel orientation of carbocyclic rings on Ag colloid particles. Therefore, when combined with HSA, the transformations of four ginsenosides still exhibit similar, although in different binding cavities in subdomain IIA and IIIA by making the methyls at C26 and C27 perpendicular plugging into the hydrophobic site of HSA, while the aglycone and glucose nearby are perpendicularly exposed outside to fit other suitable active targeting sites.
Suppression of Hepatic Cyp1a2 by Total Ginsenosides in Lipopolysaccharide-Treated Mice and Primary Mouse Hepatocytes.
Sun, Haiyan; Yan, Yijing; Xu, Chenshu; Wan, Hongxia; Liu, Dong
The roots of Panax ginseng (ginseng) have been extensively used in traditional Chinese medicine. However, herb-drug interactions between ginseng and other co-administered drugs are not fully understood concerning the effect of ginseng on drug metabolism and clearance. The current study aimed to elucidate the effect of total ginsenosides, a typical ginseng extract, on the regulation of Cyp1a2, a key enzyme to regulate drug metabolism under the normal and inflammatory conditions in mice. Female C57BL/6J mice treated with vehicle and lipopolysaccharide (LPS) were intragastrically administered ginseng extract for 7 days before hepatic P450 expression was analyzed. Primary mouse hepatocytes were also employed to further explore the effects of total ginsenosides on Cyp1a2 expression. The results showed that total ginsenosides in P. ginseng extract exhibited a concentration-dependent suppression on Cyp1a2 mRNA and protein level in both mice and primary mouse hepatocytes. Notably, the inhibitory effects of total ginsenosides on Cyp1a2 mRNA and protein expression were further enhanced following LPS treatment. Therefore, future research is warranted to investigate the role of ginsenosides in the regulation of hepatic CYP450s. Moreover, consumption of ginseng as food or supplement should be monitored for patients on combinational therapy, especially those with inflammatory diseases. PMID:26923348
Simultaneous analysis method for polar and non-polar ginsenosides in red ginseng by reversed-phase HPLC-PAD.
Lee, Sa-Im; Kwon, Ha-Jeong; Lee, Yong-Moon; Lee, Je-Hyun; Hong, Seon-Pyo
The paper describes the development of a simultaneous determination method for polar and non-polar ginsenosides in red ginseng with a reversed-phase high-performance liquid chromatography-pulsed amperometric detection method. This method could be applied directly without any pretreatment steps and enabled the performance of highly sensitive analysis within 1h. The detection (S/N=3) and quantification (S/N=10) limits for the ginsenosides ranged 0.02-0.10 ng and 0.1-0.3 ng, respectively. The linear regression coefficients ranged 0.9975-0.9998. Intra- and inter-day precisions were <9.91%. The mean recoveries ranged 98.08-103.06%. The total amount of ginsenosides in the hairy root of red ginseng was higher than that in the main root. PMID:22119615
Systematic development of a group quantification method using evaporative light scattering detector for relative quantification of ginsenosides in ginseng products.
Lee, Gwang Jin; Shin, Byong-Kyu; Yu, Yun-Hyun; Ahn, Jongsung; Kwon, Sung Won; Park, Jeong Hill
The determination for the contents of multi-components in ginseng products has come to the fore by demands of in-depth information, but the associated industries confront the high cost of securing pure standards for the continuous quality evaluation of the products. This study aimed to develop a prospective high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method for relative quantification of ginsenosides in ginseng products without a considerable change from the conventional gradient analysis. We investigated the effects of mobile phase composition and elution bandwidth, which are potential variables affecting the ELSD response in the gradient analysis. Similar ELSD response curves of nine major ginsenosides were obtained under the identical flow injection conditions, and the response increased as the percentage of organic solvent increased. The nine ginsenosides were divided into three groups to confirm the effect of elution bandwidth. The ELSD response significantly decreased in case of the late eluted ginsenoside in the individual groups under the isocratic conditions. With the consideration of the two important effects, stepwise changes of the gradient condition were carried out to reach a group quantification method. The inconsistent responses of the nine ginsenosides were reconstituted to three normalized responses by the stepwise changes of the gradient condition, and this result actualized relative quantification in the individual groups. The availability was confirmed by comparing the ginsenoside contents in a base material of ginseng products determined by the direct and group quantification method. The largest difference in the determination results from the two methods was 8.26%, and the difference of total contents was only 0.91%. PMID:27262109
Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice
Background Ginsenoside Rg3, a saponin extracted from ginseng, inhibits angiogenesis. The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice. Methods C57L/6 mice implanted with Lewis lung carcinoma were randomized into the control, ginsenoside Rg3, gemcitabine and combination group. The quality of life and survival of mice were recorded. Tumor volume, inhibitive rate and necrosis rate were estimated. Necrosis of tumor and signals of blood flow as well as dynamic parameters of arterial blood flow in tumors such as peak systolic velocity (PSV) and resistive index (RI) were detected by color Doppler ultrasound. In addition, expression of vascular endothelial cell growth factor (VEGF) and CD31 were observed by immunohistochemstry, and microvessel density (MVD) of the tumor tissues was assessed by CD31 immunohistochemical analysis. Results Quality of life of mice in the ginsenoside Rg3 and combination group were better than in the control and gemcitabine group. Combined therapy with ginsenoside Rg3 and gemcitabine not only enhanced efficacy on suppression of tumor growth and prolongation of the survival, but also increased necrosis rate of tumor significantly. In addition, the combination treatment could obviously decrease VEGF expression and MVD as well as signals of blood flow and PSV in tumors. Conclusion Ginsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice. The combination of chemotherapy and anti-angiogenic drugs may be an innovative and promising therapeutic strategy in the experimental treatment of human lung cancer. PMID:19624862
Determination of 10 ginsenosides in Panax ginseng of different harvest times based on HPLC fingerprints and principal component analysis.
Chen, Fengqin; Luo, Jianguang; Kong, Lingyi
A combinative method of HPLC fingerprinting and quantitative determination was successfully applied to monitor dynamic accumulation of ginsenosides in five-year-old Panax ginseng roots from different harvest times. The optimal chromatographic conditions were achieved on a C18 column with gradient elution using acetonitrile and 1 mmol · L(-1) KH2PO4 buffer solution at 203 nm. The result indicated that the contents of total ginsenosides showed significant variations, and a decrease tendency appeared in the growth period of the fifth year. PMID:22871218
Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative damage and bone-resorbing cytokines during osteogenesis.
Huang, Qiang; Gao, Bo; Jie, Qiang; Wei, Bo-Yuan; Fan, Jing; Zhang, Hong-Yang; Zhang, Jin-Kang; Li, Xiao-Jie; Shi, Jun; Luo, Zhuo-Jing; Yang, Liu; Liu, Jian
Reactive oxygen species (ROS) are a significant pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent antioxidant that generates interest regarding the bone metabolism area. We tested the potential anti-osteoporosis effects of Rb2 and its underlying mechanism in this study. We produced an oxidative damage model induced by hydrogen peroxide (H2O2) in osteoblastic MC3T3-E1 cells to test the essential anti-osteoporosis effects of Rb2in vitro. The results indicated that treatment of 0.1 to 10μM Rb2 promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) expression, elevated calcium mineralization and mRNA expressions of Alp, Col1a1, osteocalcin (Ocn) and osteopontin (Opn) against oxidative damage induced by H2O2. Importantly, Rb2 reduced the expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and inhibited the H2O2-induced production of ROS. The in vivo study indicated that the Rb2 administered for 12weeks partially decreased blood malondialdehyde (MDA) activity and elevated the activity of reduced glutathione (GSH) in ovariectomized (OVX) mice. Moreover, Rb2 improved the micro-architecture of trabecular bones and increased bone mineral density (BMD) of the 4th lumbar vertebrae (L4) and the distal femur. Altogether, these results demonstrated that the potential anti-osteoporosis effects of Rb2 were linked to a reduction of oxidative damage and bone-resorbing cytokines, which suggests that Rb2 might be effective in preventing and alleviating osteoporosis. PMID:24933344
Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy
Son, Keum-joo; Choi, Ki ryung; Lee, Seog Jae
Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT+ CD11c+ cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy. PMID:26937234
Ginsenosides Rg3 attenuates glucocorticoid-induced osteoporosis through regulating BMP-2/BMPR1A/Runx2 signaling pathway.
Zhang, Xiaonan; Chen, Kang; Wei, Bo; Liu, Xingwang; Lei, Zeming; Bai, Xizhuang
Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX)-induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone-alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy. PMID:27387537
Ginsenoside Rp1 Exerts Anti-inflammatory Effects via Activation of Dendritic Cells and Regulatory T Cells.
Bae, Jingyu; Koo, Jihye; Kim, Soochan; Park, Tae-Yoon; Kim, Mi-Yeon
Ginsenoside Rp1 (G-Rp1) is a saponin derivate that provides anti-metastatic activities through inhibition of the NF-κB pathway. In this study, we examined the effects of G-Rp1 on regulatory T cell (Treg) activation. After treatment of splenocytes with G-Rp1, Tregs exhibited upregulation of IL-10 expression, and along with dendritic cells (DCs), these Tregs showed increased cell number compared to other cell populations. The effect of G-Rp1 on Treg number was augmented in the presence of lipopolysaccharide (LPS), which mimics pathological changes that occur during inflammation. However, depletion of DCs prevented the increase in Treg number in the presence of G-Rp1 and/or LPS. In addition, G-Rp1 promoted the differentiation of the memory types of CD4(+)Foxp3(+)CD62L(low) Tregs rather than the generation of new Tregs. In vivo experiments also demonstrated that Tregs and DCs from mice that were fed G-Rp1 for 7 d and then injected with LPS exhibited increased activation compared with those from mice that were injected with LPS alone. Expression of TGF-β and CTLA4 in Tregs was increased, and upregulation of IL-2 and CD80/ CD86 expression by DCs affected the suppressive function of Tregs through IL-2 receptors and CTLA4. These data demonstrate that G-Rp1 exerts anti-inflammatory effects by activating Tregs in vitro and in vivo. PMID:23717139
Protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells
Fu, Wenwen; Sui, Dayun; Yu, Xiaofeng; Gou, Dongxia; Zhou, Yifa; Xu, Huali
Ginsenoside Rg2 is one of the major active components of ginseng and has many biological activities. This study aimed to investigate the protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells. The results showed that pretreatment with ginsenoside Rg2 not only increased cell viability, but also decreased lactate dehydrogenase (LDH) release. Ginsenoside Rg2 inhibited the decrease of SOD, GSH-PX activities and the increase of MDA content induced by H2O2. Meanwhile, the levels of ROS generation and cardiomyocyte apoptosis in ginsenoside Rg2 group significantly reduced when compared with the model group. Western blot analyses demonstrated that ginsenoside Rg2 up-regulate level of Bcl-2 expression and down-regulate levels of Bax, Caspase-3, -9 expression. These findings indicated that ginsenoside Rg2 could protect H9c2 cells against H2O2-induced injury through its actions of anti-oxidant and anti-apoptosis. PMID:26884906
Suppression of MAPKs/NF-κB Activation Induces Intestinal Anti-Inflammatory Action of Ginsenoside Rf in HT-29 and RAW264.7 Cells.
Ahn, Sungeun; Siddiqi, Muhammad Hanif; Aceituno, Veronica Castro; Simu, Shakina Yesmin; Yang, Deok Chun
This study investigated the intestinal anti-inflammatory action of ginsenoside Rf in inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease that affects the intestinal tract. It is associated with elevated levels of various inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and reactive oxygen species (ROS). Ginsenosides, the main active constituents of ginseng, have been reported to exert potent therapeutic effects against diverse diseases. However, ginsenoside Rf treatment for inflammation has not yet been examined. In this study, we evaluated the inhibitory effect of ginsenoside Rf on the inflammatory mediators downstream of p38/NF-kB activation on TNF-α-stimulated intestinal epithelial cells (HT-29) and mouse macrophage cells (RAW264.7). Our results showed that ginsenoside Rf significantly reduced the production of IL-1β, IL-6, TNF-α, NO, and ROS, which are most highly activated in IBD. In addition, ginsenoside Rf significantly suppressed TNF-α/LPS-induced NF-κB transcriptional activity. These results suggest that ginsenoside Rf contains a compound that has potent intestinal anti-inflammatory effects that could be used to treat diseases such as IBD. PMID:27224660
Influence of sulphur-fumigation on the quality of white ginseng: a quantitative evaluation of major ginsenosides by high performance liquid chromatography.
Jin, Xin; Zhu, Ling-Ying; Shen, Hong; Xu, Jun; Li, Song-Lin; Jia, Xiao-Bin; Cai, Hao; Cai, Bao-Chang; Yan, Ru
White ginseng was reported to be sulphur-fumigated during post-harvest handling. In the present study, the influence of sulphur-fumigation on the quality of white ginseng and its decoction were quantitatively evaluated through simultaneous quantification of 14 major ginsenosides by a validated high performance liquid chromatography. Poroshell 120 EC-C18 (100mm×3.0mm, 2.7μm) column was chosen for the separation of the major ginsenosides, which were eluted with gradient water and acetonitrile as mobile phase. The analytes were monitored by UV at 203nm. The method was validated in terms of linearity, sensitivity, precision, accuracy and stability. The sulphur-fumigated and non-fumigated white ginseng samples, as well as their respective decoctions, were comparatively analysed with the newly-validated method. It was found that the contents of nine ginsenosides detected in raw materials decreased by about 3-85%, respectively, and the total content of the nine ginsenosides detected in raw materials, decreased by almost 54% after sulphur-fumigation. On the other hand, the contents of 10 ginsenosides detected in decoctions of sulphur-fumigated white ginseng were decreased by about 33-83%, respectively, and the total content of ginsenosides was decreased by up to 64% when compared with that of non-fumigated white ginseng. In addition, ginsenoside Rh(2) and Rg(5) could be detected in the decoctions of sulphur-fumigated white ginseng but not in that of non-fumigated white ginseng. It is suggested that sulphur-fumigation can significantly influence not only the contents of original ginsenosides, but also the decocting-induced chemical transformation of ginsenosides in white ginseng. PMID:22953836
Homolog-focused profiling of ginsenosides based on the integration of step-wise formate anion-to-deprotonated ion transition screening and scheduled multiple reaction monitoring.
Song, Yuelin; Zhang, Na; Shi, Shepo; Li, Jun; Zhao, Yunfang; Zhang, Qian; Jiang, Yong; Tu, Pengfei
Homolog-focused profiling is a favored option to bridge targeted metabolomics toward non-targeted metabolomics. In current study, an attempt was made for the large-scale ginsenoside-specific analysis in ginseng (G) and American ginseng (AG). When formic acid (0.1%, v/v) was introduced as the mobile phase additive, formate anion-to-deprotonated ion transitions ([M+HCOO](-)>[M-H](-)) with an optimal collision energy (-32eV) could result in satisfactory responses for ginsenosides. Therefore, a step-wise multiple reaction monitoring (MRM)-based method employing [M+HCOO](-)>[M-H](-) ion pairs was constructed to screen ginsenosides among 501-1250u (for Q1) with a step-size of 2u, and MRM also served as a survey experiment to trigger enhanced product ion scans for MS(2) spectrum acquisition on a hybrid triple quadrupole-linear ion trap mass spectrometer; then, the identification of those observed ginsenosides was achieved on the basis of the well-defined mass cracking patterns for ginsenosides; afterwards, scheduled MRM was introduced for large-scale relatively quantitative analysis of all detected ginsenosides. Finally, comparative metabolomics were performed to differentiate G, AG, and their processed products. Method validation was carried out using thirteen authentic compounds. A total of 221 ginsenosides, among which 185 ones were annotated, were observed and relatively quantitated. All crude materials were obviously classified into groups I-III. Above all, the MRM-based homolog-focused profiling of ginsenosides could be used as a reliable tool to gain an in-depth view for ginsenoside-enriched herbal products. PMID:26105782
In Vivo Biodistribution, PET Imaging, and Tumor Accumulation of 86Y- and 111In-Antimindin/RG-1, Engineered Antibody Fragments in LNCaP Tumor–Bearing Nude Mice
Schneider, Douglas W.; Heitner, Tara; Alicke, Bruno; Light, David R.; McLean, Kirk; Satozawa, Noboru; Parry, Gordon; Yoo, Jeongsoo; Lewis, Jason S.; Parry, Renate
To optimize in vivo tissue uptake kinetics and clearance of engineered monoclonal antibody (mAb) fragments for radiotherapeutic and radiodiagnostic applications, we compared the biodistribution and tumor localization of four 111In- and 86Y-labeled antibody formats, derived from a single antimindin/RG-1 mAb, in a prostate tumor model. The IgG, diabody, single-chain variable domain (scFv), and novel miniantibody formats, composed of the human IgE-CH4 and a modified IgG1 hinge linked to scFv domains, were compared. Methods Antibodies were first derivatized with the bifunctional chelator CHX-A″-diethylenetriamine pentaacetic acid and then bound to the radiometal to create radiolabeled immunoconjugates. Human LNCaP xenografts were grown in nude mice, and 111In- or 86Y-labeled antibodies were administered intravenously. Tissues were harvested at different times, and the level of antibody deposition was determined by measuring radioactivity. Whole-body small-animal PET of mice receiving 86Y-labeled antibodies was performed at 6 time points and colocalized with simultaneous micro-CT imaging. Results The biodistributions of 111In and 86Y antibodies were quite similar. The blood, tumor, kidney, and liver tissues contained varying levels of radioactivity. The antibody accumulation in the tumor correlated with molecular size. The IgG steadily increased with time to 24.1 percentage injected dose per gram (%ID/g) at 48 h. The miniantibody accumulated at a similar rate to reach a lower level (14.2 %ID/g) at 48 h but with a higher tumor-to-blood ratio than the IgG. Tumor accumulation of the diabody peaked at 3 h, reaching a much lower level (3.7 %ID/g). A combination of rapid clearance and lower relative affinity of the scFv precluded deposition in the tumor. Small-animal PET results correlated well with the biodistribution results, with similar tumor localization patterns. Conclusion The larger antibody formats (IgG and miniantibody) gave higher tumor uptake levels than did the
Comparative study on intestinal metabolism and absorption in vivo of ginsenosides in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid chromatography quadruple time-of-flight mass spectrometry based chemical profiling approach.
Zhu, He; Shen, Hong; Xu, Jun; Xu, Jin-Di; Zhu, Ling-Ying; Wu, Jie; Chen, Hu-Biao; Li, Song-Lin
Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated. PMID:24853104
Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS.
Yoon, Sung-Jin; Park, Jun-Young; Choi, Song; Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo; Shim, Sungbo; Park, Young-Jun
Ginsenoside Rg3, a specific biological effector, is well-known as a major bioactive ingredient of Panax ginseng. However, its role in the inflammasome activation process remains unclear. In this report, we demonstrate that ginsenosides 20(R)-Rg3 and 20(S)-Rg3 are capable of suppressing both lethal endotoxic shock and the S-nitrosylation of the NLRP3 inflammasome by inhibiting nitric oxide (NO) production through the regulation of inducible nitric oxide synthase (iNOS) expression. In response to lipopolysaccharide (LPS), the reducing effect of 20(S)-Rg3 and 20(R)-Rg3 on nitric oxide led to an increase in the survival time of mice after lethal endotoxin-induced shock, and excess levels of NO inhibited IL-1β production via the S-nitrosylation of the NLRP3 inflammasome. In addition, ginsenosides 20(R)-Rg3 and 20(S)-Rg3 had suppressive effects on the LPS- or UV-irradiation-induced reactive oxygen species (ROS) levels in macrophage and HaCaT cells and thereby prevented apoptosis of spleen cells in mice. Altogether, these results demonstrate that ginsenoside 20(R)-Rg3 and 20(S)-Rg3, a naturally occurring compound, might act as a dual therapeutic regulator for the treatment of inflammatory and oxidative stress-related diseases. PMID:26086107
Effects of ginsenosides, the active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans
Technology Transfer Automated Retrieval System (TEKTRAN)
Ginsenosides, the active ingredients of Panax ginseng, are saponins derived from sterols. The free-living nematode Caenorhabditis elegans is a well-established model for biochemical and genetic studies in animals. Although cholesterol is an essential requirement for the growth and development of C. ...
Metabolomic investigation of the anti-platelet aggregation activity of ginsenoside Rk₁ reveals attenuated 12-HETE production.
Ju, Hyun Kyoung; Lee, Jin Gyun; Park, Mi Kyung; Park, So-Jung; Lee, Chang Hoon; Park, Jeong Hill; Kwon, Sung Won
Comprehensive metabolomics analysis is an effective method of measuring metabolite levels in the body following administration of a pharmaceutical compound and can allow for monitoring of the effects of the compound or assessment of appropriate treatment options for individual patients. In the present metabolomics study, samples pretreated with antiplatelet compounds were extracted and subjected to ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. The acquired data were processed using peak clustering and evaluated by partial least-squares (PLS) and orthogonal projections to latent structures discriminant analyses (OPLS-DA). As a result, meaningful endogenous metabolites, namely eicosanoids and thromboxane B(2) (TXB(2)), were identified. TXB(2), a key element in platelet aggregation, was decreased upon ginsenoside Rk(1) treatment via inhibition of cyclooxygenase (COX) activity. One of the arachidonic acid (AA) metabolites, 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), was decreased significantly in the ginsenoside Rk(1)-treated platelets compared to the AA-induced group. In the mechanism study of ginsenoside Rk(1), a strong linkage to intracellular calcium levels, which induce platelet activation, was found. Additionally, the translocation of 12-LOX from cytosol to membrane, which is related with the intracellular calcium levels, was determined. Therefore, a decreased 12-HETE level induced by ginsenoside Rk(1) on antiplatelet aggregation is related to 12-LOX translocation resulting from decreased Ca(2+) levels. This study shows that global metabolomic analysis has potential for use in understanding the biological behavior of antiplatelet drugs. PMID:22873173
[Study on the Effects of Ginsenoside Rb1 on DPPC Bilayers by Using Thermo-Raman Spectrum and DSC].
Hui, Ge; Liu, Wei; Zhang, Jing-zhou; Zhou, Tie-li; Wang, Si-ming; Zhao, Yu; Zhao, Bing
The research on the interactions between Ginsenosides and biomembranes plays a crucial role in thorough understanding the pharmacological activity and biologyical effect of Chinese medicine Panax ginseng. With the bilayer structure, DPPC often serves as an simulation model of the cell membrane to study the role of drug molecules and cell membranes. Ginsenoside Rb1, one of the most important components of Panaxginseng, playing the significant roles of pharmacological effects and biological properties. Raman and differential scanning calorimetry (DSC) are respectively a powerful tool for discussing the molecular interaction, and a kind of general technology by which researching the bilayer monomer structures and its interactions with drug molecules. However, rarely research reports on the interactions between drug molecules and biomembranes by means of both technologies above. In this paper, the influence of ginsenoside monomer Rb1 on DPPC membrane bilayers was investigated by thermo-Raman and DSC. In Raman spectra, the changes of DPPC molecule have been observed before and after interacted with ginsenoside Rb1, the data analysis indicates three aspects: the O-C-C-N+ polar head group skeleton, C-C stretching vibration area, and the C-H bond stretching vibrarion in terminated methyl group of alkyl chains. The results showed that ginsenoside Rb1 molecule with certain concentration has not changed the gauche conformation of the polar head backbone group in DPPC bilayers, the order of the internal molecular chain and the lateral chain-chain packing have been decreased as the temperature increased, the lateral disposed disorder has been increased. The changes of some thermodynamic constants obtained by DSC experiment such as phase transition temperature (Tm), the temperature at which the transition is half completed (ΔT1/2), and the transition enthalpy normalized per mol of DPPC (AH) have been showed further results of the thermo Raman experiments, with increasing the
Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites
Chen, Xiao-Jia; Zhang, Xiao-Jing; Shui, Yan-Mei; Wan, Jian-Bo
Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer. PMID:27446225
Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice
Qi, Bo; Zhang, Lan; Zhang, Zhiqun; Ouyang, Jiangqiong; Huang, Hui
Background: The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice. Materials and Methods: A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured. Results: The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice. Conclusions: The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice. PMID:25422546
The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation
Chen, Fang; Zhang, Bing; Sun, Yong; Xiong, Zeng-Xing; Peng, Han; Deng, Ze-Yuan; Hu, Jiang-Ning
Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome. PMID:27120618
Ginsenoside Rb1: the anti-ulcer constituent from the head of Panax ginseng.
Jeong, Choon Sik; Hyun, Jin Ee; Kim, Yeong Shik
We previously reported that the butanol (BuOH) fraction of the head of Panax ginseng exhibited gastroprotective activity in peptic and chronic ulcer models. In order to identify the active constituent, an activity-guided isolation of the BuOH faction was conducted with a HCl x ethanol-induced gastric lesion model. The BuOH fraction was passed through a silica-gel column using a chloroform-methanol gradient solvent system, and six fractions (frs. 1-6) were obtained. The active fr. 5 was further separated by silica-gel column, to yield 6 subfractions (subfrs. a-f). Subfr. d was composed of ginsenosides Re, Rc and Rb1. The most active constituent was ginsenoside Rb1 (GRb1), a protopanaxadiol glycoside, which was investigated for its anti-ulcer effect. Gastric injury induced by HCl x ethanol, indomethacin and pyloric ligation (Shay ulcer) was apparently reduced with oral GRb1 doses of 150 and 300 mg/kg. GRb1 at these dosage significantly increased the amount of mucus secretion in an ethanol-induced model. The anti-ulcer effects were consistent with the result of histological examination. These results suggest that the major active constituent in the head of Panax ginseng is GRb1, and that anti-ulcer effect is produced through an increase in mucus secretion. PMID:14661855
Optimization of lipase-catalyzed synthesis of ginsenoside Rb1 esters using response surface methodology.
Hu, Jiang-Ning; Lee, Jeung-Hee; Zhu, Xue-Mei; Shin, Jung-Ah; Adhikari, Prakash; Kim, Jae-Kyung; Lee, Ki-Teak
In the lipase (Novozyme 435)-catalyzed synthesis of ginsenoside Rb1 esters, different acyl donors were found to affect not only the degree of conversion but also the regioselectivity. The reaction of acyl donors with short carbon chain was more effective, showing higher conversion than those with long carbon chain. Among the three solvent systems, the reaction in tert-amyl alcohol showed the highest conversion rate, while the reaction in the mixed solvent of t-BuOH and pyridine (1:1) had the lowest conversion rate. To allow the increase of GRb1 lipophilicity, we decided to further study the optimal condition of synthesis of GRb1 with vinyl decanoate with 10 carbon chain fatty acids in tert-amyl alcohol. Response surface methodology (RSM) was employed to optimize the synthesis condition. From the ridge analysis with maximum responses, the maximum GRb1 conversion was predicted to be 61.51% in a combination of factors (40.2 h, 52.95 degrees C, substrate mole ratio 275.57, and enzyme amount 39.81 mg/mL). Further, the adequacy of the predicted model was examined by additional independent experiments at the predicted maximum synthesis conditions. Results showed that the RSM was effective to optimize a combination of factors for lipase-catalyzed synthesis of ginsenoside Rb1 with vinyl decanoate. PMID:18983161
Anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells.
Lee, Yu Young; Park, Jin-Sun; Jung, Ji-Sun; Kim, Dong-Hyun; Kim, Hee-Sun
Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1b, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-kB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders. PMID:23698769
The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation.
Chen, Fang; Zhang, Bing; Sun, Yong; Xiong, Zeng-Xing; Peng, Han; Deng, Ze-Yuan; Hu, Jiang-Ning
Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome. PMID:27120618
Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites.
Chen, Xiao-Jia; Zhang, Xiao-Jing; Shui, Yan-Mei; Wan, Jian-Bo; Gao, Jian-Li
Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer. PMID:27446225
Rk1, a ginsenoside, is a new blocker of vascular leakage acting through actin structure remodeling.
Maeng, Yong-Sun; Maharjan, Sony; Kim, Jeong-Hun; Park, Jeong-Hill; Suk Yu, Young; Kim, Young-Myoung; Kwon, Young-Guen
Endothelial barrier integrity is essential for vascular homeostasis and increased vascular permeability and has been implicated in many pathological processes, including diabetic retinopathy. Here, we investigated the effect of Rk1, a ginsenoside extracted from sun ginseng, on regulation of endothelial barrier function. In human retinal endothelial cells, Rk1 strongly inhibited permeability induced by VEGF, advanced glycation end-product, thrombin, or histamine. Furthermore, Rk1 significantly reduced the vessel leakiness of retina in a diabetic mouse model. This anti-permeability activity of Rk1 is correlated with enhanced stability and positioning of tight junction proteins at the boundary between cells. Signaling experiments revealed that Rk1 induces phosphorylation of myosin light chain and cortactin, which are critical regulators for the formation of the cortical actin ring structure and endothelial barrier. These findings raise the possibility that ginsenoside Rk1 could be exploited as a novel prototype compound for the prevention of human diseases that are characterized by vascular leakage. PMID:23894330
Localization of ginsenosides in Panax ginseng with different age by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry imaging.
Bai, Hangrui; Wang, Shujuan; Liu, Jianjun; Gao, Dan; Jiang, Yuyang; Liu, Hongxia; Cai, Zongwei
The root of Panax ginseng C.A. Mey. (P. ginseng) is one of the most popular traditional Chinese medicines, with ginsenosides as its main bioactive components. Because different ginsenosides have varied pharmacological effects, extraction and separation of ginsenosides are usually required for the investigation of pharmacological effects of different ginsenosides. However, the contents of ginsenosides vary with the ages and tissues of P. ginseng root. In this research, an efficient method to explore the distribution of ginsenosides and differentiate P. ginseng roots with different ages was developed based on matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI). After a simple sample preparation, there were 18 peaks corresponding to 31 ginsenosides with distinct localization in the mass range of m/z 700-1400 identified by MALDI-TOF-MSI and MALDI-TOF-MS/MS. All the three types of ginsenosides were successfully detected and visualized in images, which could be correlated with anatomical features. The P. ginseng at the ages of 2, 4 and 6 could be differentiated finely through the principal component analysis of data collected from the cork based on the ion images but not data from the whole tissue. The experimental result implies that the established method for the direct analysis of metabolites in plant tissues has high potential for the rapid identification of metabolites and analysis of their localizations in medicinal herbs. Furthermore, this technique also provides valuable information for the component-specific extraction and pharmacological research of herbs. PMID:26520809
Identification of ginsenoside markers from dry purified extract of Panax ginseng by a dereplication approach and UPLC-QTOF/MS analysis.
Yang, Heejung; Lee, Dong Young; Kang, Kyo Bin; Kim, Jeom Yong; Kim, Sun Ok; Yoo, Young Hyo; Sung, Sang Hyun
A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing process that includes column chromatography, acid hydrolysis, and an enzyme reaction. During the manufacturing process, the more polar ginsenosides were altered into less polar forms via cleavage of their sugar chains and structural modifications of the aglycones, such as hydroxylation and dehydroxylation. The structural changes of ginsenosides during the intermediate steps from dried ginseng extract (DGE) to PEG were monitored by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC-QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards for determining of unknown ginsenosides and further suggesting of the metabolic markers. The elution order of 22 ginsenosides based on the type of aglycones, and the location and number of sugar chains can be used for the structural elucidation of unknown ginsenosides. This information could be used in a dereplication process for quick and efficient identification of ginsenoside derivatives in ginseng preparations. A dereplication approach helped the identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during the conversion process with multivariate analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) plots. These metabolic markers were identified by comparing with the dereplication information of the reference standards of 22 ginsenosides, or they were assigned using the pattern of the MS/MS fragmented ions. Consequently, the developed metabolic profiling approach using UPLC-QTOF/MS and multivariate analysis represents a new method for providing quality control as well as useful criteria for a similarity evaluation of the manufacturing process of ginseng preparations. PMID:25767906
Metabolism of ginsenosides Rk₃ and Rh₄ from steamed notoginseng in zebrafish by ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry.
Chen, Bin; Wei, Yingjie; Wang, Dandan; Jia, Xiaobin
In this work, the metabolite profiles of ginsenosides Rk3 and Rh4 from steamed notoginseng in zebrafish were qualitatively investigated, and their possible metabolic pathways were subsequently proposed. Metabolites of ginsenosides Rk3 and Rh4 after exposing to zebrafish for 24 h were identified by Ultraperformance Liquid Chromatography/Quadrupole -Time-of-Flight Mass Spectrometry (UPLC-TOF/MS). The separation was performed with a UPLC BEH C18 column using a binary gradient elution of 0.1 % formic acetonitrile -0.1 % formic acid water. The quasi-molecular ions of compounds were detected in negative mode. According to the quasi-molecular ions and MS2 spectra, after comparison with reference standards, molecular mass information and the potential structures about metabolites of ginsenosides Rk3 and Rh4 were obtained. In all, 5 and 6 metabolites of ginsenoside Rk3 and Rh4 including M1(M6), M2(M7), M3-M5 and N1, N2(N7), N3-N6 were identified in zebrafish respectively, which were to our knowledge reported for the first time. The results indicated that ginsenosides Rk3 and Rh4 were metabolized via desugarization, glucuronidation, sulfation, dehydroxylation, and loss of C-17 and C-23 residue pathways in zebrafish. Loss of glucose at position C-6 and glucuronidation at position C-3 or C-6 in zebrafish were considered as the main physiologic processes of ginsenosides Rk3 and Rh4. PMID:25547981
Changes of ginsenoside content by mushroom mycelial fermentation in red ginseng extract.
Bae, Song Hwan; Lee, Hyun-Sun; Kim, Mi-Ryung; Kim, Sun Young; Kim, Jin-Man; Suh, Hyung Joo
To obtain microorganisms for the microbial conversion of ginsenosides in red ginseng extract (RGE), mushroom mycelia were used for the fermentation of RGE. After fermentation, total sugar contents and polyohenol contents of the RGEs fermented with various mushrooms were not a significant increase between RGE and the ferments. But uronic acid content was relatively higher in the fermented RGEs cultured with Lentus edodes (2155.6 μg/mL), Phelllinus linteus (1690.9 μg/mL) and Inonotus obliquus 26137 and 26147 (1549.5 and 1670.7 μg/mL) compared to the RGE (1307.1 μg/mL). The RGEs fermented by Ph. linteus, Cordyceps militaris, and Grifola frondosa showed particularly high levels of total ginsenosides (20018.1, 17501.6, and 16267.0 μg/mL, respectively). The ferments with C. militaris (6974.2 μg/mL), Ph. linteus (9109.2 μg/mL), and G. frondosa (7023.0 μg/mL) also showed high levels of metabolites (sum of compound K, Rh1, Rg5, Rk1, Rg3, and Rg2) compared to RGE (3615.9 μg/mL). Among four different RGE concentrations examined, a 20 brix concentration of RGE was favorable for the fermentation of Ph. linteus. Maximum biotransformation of ginsneoside metabolites (9395.5 μg/mL) was obtained after 5 days fermentation with Ph. linteus. Maximum mycelial growth of 2.6 mg/mL was achieved at 9 days, in which growth was not significantly different during 5 to 9 days fermentation. During fermentation of RGE by Ph. linteus in a 7 L fermenter, Rg3, Rg5, and Rk1 contents showed maximum concentrations after 5 days similar to flask fermentation. These results confirm that fermentation with Ph. linteus is very useful for preparing minor ginsenoside metabolites while being safe for foods. PMID:23717066
Ginsenoside Rb3 protects cardiomyocytes against ischemia-reperfusion injury via the inhibition of JNK-mediated NF-κB pathway: a mouse cardiomyocyte model.
Ma, Lijia; Liu, Huimin; Xie, Zulong; Yang, Shuang; Xu, Wei; Hou, Jingbo; Yu, Bo
Ginsenoside Rb3 is extracted from the plant Panax ginseng and plays important roles in cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury. NF-κB is an important transcription factor involved in I/R injury. However, the underlying mechanism of ginsenoside Rb3 in myocardial I/R injury remains poorly understood. In the current study, a model of myocardial I/R injury was induced via oxygen and glucose deprivation (OGD) followed by reperfusion (OGD-Rep) in mouse cardiac myoblast H9c2 cells. Our data demonstrate that ginsenoside Rb3 suppresses OGD-Rep-induced cell apoptosis by the suppression of ROS generation. By detecting the NF-κB signaling pathway, we discover that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is closely related to the inhibition of NF-κB activity. Ginsenoside Rb3 inhibits the upregulation of phospho-IκB-α and nuclear translocation of NF-κB subunit p65 which are induced by ORD-Rep injury. In addition, the extract also inhibits the OGD-Rep-induced increase in the expression of inflammation-related factors, such as IL-6, TNF-α, monocyte chemotactic protein-1 (MCP-1), MMP-2 and MMP-9. However, LPS treatment alleviates the protective roles of ginsenoside Rb3 and activates the NF-κB pathway. Finally, the upstream factors of NF-κB were analyzed, including the Akt/Foxo3a and MAPK signaling pathways. We find that ginsenoside Rb3 pretreatment only decreases the phosphorylation of JNK induced by OGD-Rep injury, an indicator of the MAPK pathway. Importantly, an inhibitor of phospho-JNK, SP600125, protects against OGD-Rep induced apoptosis and inhibited NF-κB signaling pathway, similar to the roles of ginsenoside Rb3. Taken together, our results demonstrate that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is attributed to the inhibition of JNK-mediated NF-κB activation, suggesting that ginsenoside Rb3 has the potential to serve as a novel therapeutic agent for myocardial I/R injury. PMID
Ginsenoside Rb3 Protects Cardiomyocytes against Ischemia-Reperfusion Injury via the Inhibition of JNK-Mediated NF-κB Pathway: A Mouse Cardiomyocyte Model
Xie, Zulong; Yang, Shuang; Xu, Wei; Hou, Jingbo; Yu, Bo
Ginsenoside Rb3 is extracted from the plant Panax ginseng and plays important roles in cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury. NF-κB is an important transcription factor involved in I/R injury. However, the underlying mechanism of ginsenoside Rb3 in myocardial I/R injury remains poorly understood. In the current study, a model of myocardial I/R injury was induced via oxygen and glucose deprivation (OGD) followed by reperfusion (OGD-Rep) in mouse cardiac myoblast H9c2 cells. Our data demonstrate that ginsenoside Rb3 suppresses OGD-Rep-induced cell apoptosis by the suppression of ROS generation. By detecting the NF-κB signaling pathway, we discover that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is closely related to the inhibition of NF-κB activity. Ginsenoside Rb3 inhibits the upregulation of phospho-IκB-α and nuclear translocation of NF-κB subunit p65 which are induced by ORD-Rep injury. In addition, the extract also inhibits the OGD-Rep-induced increase in the expression of inflammation-related factors, such as IL-6, TNF-α, monocyte chemotactic protein-1 (MCP-1), MMP-2 and MMP-9. However, LPS treatment alleviates the protective roles of ginsenoside Rb3 and activates the NF-κB pathway. Finally, the upstream factors of NF-κB were analyzed, including the Akt/Foxo3a and MAPK signaling pathways. We find that ginsenoside Rb3 pretreatment only decreases the phosphorylation of JNK induced by OGD-Rep injury, an indicator of the MAPK pathway. Importantly, an inhibitor of phospho-JNK, SP600125, protects against OGD-Rep induced apoptosis and inhibited NF-κB signaling pathway, similar to the roles of ginsenoside Rb3. Taken together, our results demonstrate that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is attributed to the inhibition of JNK-mediated NF-κB activation, suggesting that ginsenoside Rb3 has the potential to serve as a novel therapeutic agent for myocardial I/R injury. PMID
Melanin Biosynthesis Inhibition Effects of Ginsenoside Rb2 Isolated from Panax ginseng Berry.
Lee, Dae Young; Jeong, Yong Tae; Jeong, Sang Chul; Lee, Mi Kyoung; Min, Jin Woo; Lee, Jae Won; Kim, Geum Soog; Lee, Seung Eun; Ahn, Young Sup; Kang, Hee Cheol; Kim, Jin Hee
Ginsenoside Rb2 (Gin-Rb2) was purified from the fruit extract of Panax ginseng. Its chemical structure was measured by spectroscopic analysis, including HR-FAB-MS, (1)H-NMR, and IR spectroscopy. Gin-Rb2 decreased potent melanogenesis in melan-a cells, with 23.4% at 80 μM without cytotoxicity. Gin-Rb2 also decreased tyrosinase and MITF protein expression in melan-a cells. Furthermore, Gin-Rb2 presented inhibition of the body pigmentation in the zebrafish in vivo system and reduced melanin contents and tyrosinase activity. These results show that Gin-Rb2 isolated from P. ginseng may be an effective skin-whitening agent via the in vitro and in vivo systems. PMID:26437949
Single-run HPLC/ESI-LITMS profiling of ginsenosides in plant extracts and ginseng based products.
Stavrianidi, Andrey; Rodin, Igor; Braun, Arkady; Stekolshchikova, Elena; Shpigun, Oleg
A rapid single-run analytical approach suitable to achieve a comprehensive characterization of ginsenosides - the main bioactive compounds present in plant materials from Panax species and ginseng-based products - was developed. The method is based on high-performance liquid chromatography coupled with electrospray positive ionization linear ion trap mass spectrometry (HPLC/ESI-LITMS). The main ions in the ESI-LITMS spectra were attributed to molecular adducts with sodium and potassium and fragments corresponding to cleavage of the glycosidic bonds. The simplicity of the approach allows laborious sample preparation and sophisticated spectral information-dependent acquisition to be avoided, and provides an opportunity for rapid screening. The method may replace existing HPLC-DAD profiling approaches. The results of this study indicate that HPLC/ESI-LITMS is applicable for quality control purposes on processed products and allows the rapid and direct identification of ginsenosides in crude plant extracts. PMID:25355704
Panax ginseng Adventitious Root Suspension Culture: Protocol for Biomass Production and Analysis of Ginsenosides by High Pressure Liquid Chromatography.
Murthy, Hosakatte Niranjana; Paek, Kee Yoeup
Panax ginseng C.A. Meyer (Korean ginseng) is a popular herbal medicine. It has been used in Chinese and Oriental medicines since thousands of years. Ginseng products are generally used as a tonic and an adaptogen to resist the adverse influence of a wide range of physical, chemical and biological factors, and to restore homeostasis. Ginsenosides or ginseng saponins are the principal active ingredients of ginseng. Since ginseng cultivation process is very slow and needs specific environment for field cultivation, cell and tissue cultures are sought as alternatives for the production of ginseng biomass and bioactive compounds. In this chapter, we focus on methods of induction of adventitious roots from ginseng roots, establishment of adventitious root suspension cultures using bioreactors, procedures for processing of adventitious roots, and analysis of ginsenosides by high pressure liquid chromatography. PMID:27108314
A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on Alzheimer disease mouse model.
Gong, Yingge; Liu, Ying; Zhou, Ling; Di, Xin; Li, Wei; Li, Qing; Bi, Kaishun
A metabonomic method was established to find potential biomarkers and study the metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as potential agent in neuroprotection and anti-inflammation, was also studied to learn the regulation mechanism to plasma metabolites in model animals. In experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal model. After drug administration, animals were evaluated by Morris water maze behavior test and sacrificed. Plasma samples were then analyzed using UHPLC-TOF/MS method to determine the endogenous metabolites. Behavior test results revealed that the spatial learning and memory abilities were deficit in model mice, and total ginsenosides could improve cognition abilities in dose-dependent manners. Principal component analysis showed that model and sham were divided into two groups, which means the metabolic network of mice was disturbed after modeling. Accordingly, 19 biomarkers were found and identified. In model group, the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1), LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine, phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The levels of these metabolites were recovered in different degrees after total ginsenosides administration. Combining with behavior study results, total ginsenosides could ameliorate both cognition symptoms and metabolic changes in model animals. This metabonomic approach provided a feasible way to understand the endogenous alterations of AD and to study the pharmacodynamic activity of novel agents. PMID:26210744
Ginsenoside Rg3 Enhances Large Conductance Ca2+-Activated Potassium Channel Currents: A Role of Tyr360 Residue
Choi, Sun-Hye; Shin, Tae-Joon; Lee, Byung-Hwan; Hwang, Sung Hee; Lee, Sang-Mok; Lee, Byung-Cheol; Park, Cheol-Seung; Ha, Tal Soo; Nah, Seung-Yeol
Ginsenosides, active ingredients of Panax ginseng, are known to exhibit neuroprotective effects. Large-conductance Ca2+-activated K+ (BKCa) channels are key modulators of cellular excitability of neurons and vascular smooth muscle cells. In the present study, we examined the effects of ginsenosides on rat brain BKCa (rSlo) channel activity heterologously expressed in Xenopus oocytes to elucidate the molecular mechanisms how ginsenoside regulates the BKCa channel activity. Ginsenoside Rg3 (Rg3) enhanced outward BKCa channel currents. The Rg3-enhancement of outward BKCa channel currents was concentration-dependent, voltage-dependent, and reversible. The EC50 was 15.1 ± 3.1 μM. Rg3 actions were not desensitized by repeated treatment. Tetraetylammonium (TEA), a K+ channel blocker, inhibited BKCa channel currents. We examined whether extracellular TEA treatment could alter the Rg3 action and vice versa. TEA caused a rightward shift of the Rg3 concentration-response curve (i.e., much higher concentration of Rg3 is required for the activation of BKCa channel compared to the absence of TEA), while Rg3 caused a rightward shift of the TEA concentration-response curve in wild-type channels. Mutation of the extracellular TEA binding site Y360 to Y360I caused a rightward shift of the TEA concentration-response curve and almost abolished both the Rg3 action and Rg3-induced rightward shift of TEA concentration-response curve. These results indicate that Tyr360 residue of BKCa channel plays an important role in the Rg3-enhancement of BKCa channel currents. PMID:21191818
Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue
Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo
Objective: This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Methods: Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral "Pishu" once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Results: Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes and correct CD4+/CD8+ ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Conclusions: Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively. PMID:26770528
Proteomic Analyses Provide Novel Insights into Plant Growth and Ginsenoside Biosynthesis in Forest Cultivated Panax ginseng (F. Ginseng)
Ma, Rui; Sun, Liwei; Chen, Xuenan; Mei, Bing; Chang, Guijuan; Wang, Manying; Zhao, Daqing
F. Ginseng (Panax ginseng) is planted in the forest to enhance the natural ginseng resources, which have an immense medicinal and economic value. The morphology of the cultivated plants becomes similar to that of wild growing ginseng (W. Ginseng) over the years. So far, there have been no studies highlighting the physiological or functional changes in F. Ginseng and its wild counterparts. In the present study, we used proteomic technologies (2DE and iTRAQ) coupled to mass spectrometry to compare W. Ginseng and F. Ginseng at various growth stages. Hierarchical cluster analysis based on protein abundance revealed that the protein expression profile of 25-year-old F. Ginseng was more like W. Ginseng than less 20-year-old F. Ginseng. We identified 192 differentially expressed protein spots in F. Ginseng. These protein spots increased with increase in growth years of F. Ginseng and were associated with proteins involved in energy metabolism, ginsenosides biosynthesis, and stress response. The mRNA, physiological, and metabolic analysis showed that the external morphology, protein expression profile, and ginsenoside synthesis ability of the F. Ginseng increased just like that of W. Ginseng with the increase in age. Our study represents the first characterization of the proteome of F. Ginseng during development and provides new insights into the metabolism and accumulation of ginsenosides. PMID:26858731
Ginsenoside Rd attenuates Aβ25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons.
Liu, Juan-fang; Yan, Xiao-dong; Qi, Lin-song; Li, Ling; Hu, Geng-yao; Li, Peng; Zhao, Gang
One of the most common pathological changes in Alzheimer's disease (AD) brain is the large number of amyloid β (Aβ) peptides accumulating in lesion areas. Ginsenosides are the most active components extracted from ginseng. Ginsenoside Rd (GRd) is a newly discovered saponin that has a stronger pharmacological activity than other ginsenosides, especially in neuroprotection. Here we examined the neuroprotective effects of GRd against neuronal insults induced by Aβ25-35 in primary cultured hippocampal neurons. A 10μM GRd treatment significantly prevented the loss of hippocampal neurons induced by Aβ25-35. In addition, GRd significantly ameliorated Aβ25-35-induced oxidative stress by decreasing the reactive oxygen species (ROS) production and malondialdehyde (MDA) level, and increasing the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); which is similar in treatments with 10μM of probucol (PB) and 100μM of edaravone (EDA). Moreover, our present study demonstrated that GRd significantly enhanced the expression of Bcl-2 mRNA, and decreased the expressions of Bax mRNA and Cyt c mRNA. GRd also downregulated the protein level of cleaved Caspase-3 compared to controls. These results highlighted the neuroprotective effects of GRd against Aβ25-35-induced oxidative stress and neuronal apoptosis, suggesting that this may be a promising therapeutics against AD. PMID:26111763
Protective properties of ginsenoside Rb1 against UV-B radiation-induced oxidative stress in human dermal keratinocytes.
Oh, Sun-Joo; Kim, Kyunghoon; Lim, Chang-Jin
Ginsenosides, also known as ginseng saponins, are responsible for most pharmacological effect of ginseng. Ginsenoside Rb1 (Rb1) exerts a variety of pharmacological properties, including anti-inflammatory, antistress, anti-aging and anti-neurodegenerative activities. The aim of the present work was to assess the skin anti-photoaging properties of Rb1 in human dermal keratinocyte HaCaT cells. The anti-photoaging activity was evaluated by analyzing the levels of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) as well as cell viability for HaCaT cells under UV-B irradiation. Rb1 was able to suppress the ROS levels which were elevated under UV-B irradiation, and unable to influence cellular survival in UV-B-irradiated HaCaT cells. Rb1 diminished the enhancement of MMP-2 gelatinolytic activity in conditioned medium, which corresponded with the decreased MMP-2 protein levels in both conditioned medium and cellular lysate prepared from UV-B-irradiated HaCaT cultures. Rb1 could restore the total glutathione (GSH) and superoxide dismutase (SOD) activity diminished in UV-B-irradiated HaCaT cells. Ginsenoside Rb1 possesses skin anti-photoaging properties through scavenging ROS and decreasing MMP-2 levels possibly by enhancing antioxidant activity in keratinocytes under UV-B irradiation. PMID:26189299
Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53.
Li, Binghui; Zhao, Jiong; Wang, Chong-Zhi; Searle, Jennifer; He, Tong-Chuan; Yuan, Chun-Su; Du, Wei
Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2-induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anti-cancer effect of Rh2 can be enhanced by antioxidants. PMID:21194832
Proteomic analysis of ginsenoside Re attenuates hydrogen peroxide-induced oxidative stress in human umbilical vein endothelial cells.
Huang, Gui-Dong; Zhong, Xian-Feng; Deng, Ze-Yuan; Zeng, Rong
Ginsenoside Re is an active component in ginseng that has attracted much attention because of its evident therapeutic effects on the cardiovascular system. However, little basic information is available on the mechanisms and pharmacological effects of ginsenoside Re. The potential mechanisms and protective effects of Re on H2O2-induced oxidative injury in human umbilical vein endothelial cells (HUVECs) were investigated in this study. An oxidative injury model was established using H2O2. The anti-oxidative effects of Re were determined using a series of experiments, such as MTT and anti-oxidative indicator assays. The potential protective mechanisms of Re were explored at the proteomic level, and differentially expressed proteins were validated by quantitative real-time polymerase chain reaction and western blotting. Results indicated that Re could be a potential anti-oxidant to protect HUVECs against oxidative stress damage. Proteomic analysis showed that the expression of 23 protein spots was upregulated in Re and H2O2 groups to resist oxidative stress, 15 of which were identified by their mass spectrum. These upregulated proteins were involved in stress response, anti-oxidative systems, protein synthesis, regulation of transcription and post-translational modifications, and repair of mitochondrial functions. This study may provide new insights into the mechanisms of ginsenoside Re in protecting the cardiovascular system. PMID:27161858
The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice
Kim, Ki-Suk; Jung Yang, Hea; Lee, In-Seung; Kim, Kang-Hoon; Park, Jiyoung; Jeong, Hyeon-Soo; Kim, Yoomi; Seok Ahn, Kwang; Na, Yun-Cheol; Jang, Hyeung-Jin
Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Gαgust−/− mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI-H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model. PMID:26675132
Structure-Activity Relationship and Substrate-Dependent Phenomena in Effects of Ginsenosides on Activities of Drug-Metabolizing P450 Enzymes
Hao, Miao; Zhao, Yuqing; Chen, Peizhan; Huang, He; Liu, Hong; Jiang, Hualiang; Zhang, Ruiwen; Wang, Hui
Ginseng, a traditional herbal medicine, may interact with several co-administered drugs in clinical settings, and ginsenosides, the major active components of ginseng, may be responsible for these ginseng-drug interactions (GDIs). Results from previous studies on ginsenosides' effects on human drug-metabolizing P450 enzymes are inconsistent and confusing. Herein, we first evaluated the inhibitory effects of fifteen ginsenosides and sapogenins on human CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 enzymes by using commercially available fluorescent probes. The structure-activity relationship of their effects on the P450s was also explored and a pharmacophore model was established for CYP3A4. Moreover, substrate-dependent phenomena were found in ginsenosides' effects on CYP3A4 when another fluorescent probe was used, and were further confirmed in tests with conventional drug probes and human liver microsomes. These substrate-dependent effects of the ginsenosides may provide an explanation for the inconsistent results obtained in previous GDI reports. PMID:18628990
Bioconversion of ginsenosides Rb(1), Rb(2), Rc and Rd by novel β-glucosidase hydrolyzing outer 3-O glycoside from Sphingomonas sp. 2F2: cloning, expression, and enzyme characterization.
Wang, Liang; Liu, Qing-Mei; Sung, Bong-Hyun; An, Dong-Shan; Lee, Hyung-Gwan; Kim, Song-Gun; Kim, Sun-Chang; Lee, Sung-Taik; Im, Wan-Taek
A new β-glucosidase gene (bglSp) was cloned from the ginsenoside converting Sphingomonas sp. strain 2F2 isolated from the ginseng cultivating filed. The bglSp consisted of 1344 bp (447 amino acid residues) with a predicted molecular mass of 49,399 Da. A BLAST search using the bglSp sequence revealed significant homology to that of glycoside hydrolase superfamily 1. This enzyme was overexpressed in Escherichia coli BL21 (DE3) using a pET21-MBP (TEV) vector system. Overexpressed recombinant enzymes which could convert the ginsenosides Rb(1), Rb(2), Rc and Rd to the more pharmacological active rare ginsenosides gypenoside XVII, ginsenoside C-O, ginsenoside C-Mc(1) and ginsenoside F(2), respectively, were purified by two steps with Amylose-affinity and DEAE-Cellulose chromatography and characterized. The kinetic parameters for β-glucosidase showed the apparent K(m) and V(max) values of 2.9±0.3 mM and 515.4±38.3 μmol min(-1)mg of protein(-1) against p-nitrophenyl-β-d-glucopyranoside. The enzyme could hydrolyze the outer C3 glucose moieties of ginsenosides Rb(1), Rb(2), Rc and Rd into the rare ginsenosides Gyp XVII, C-O, C-Mc(1) and F(2) quickly at optimal conditions of pH 5.0 and 37°C. A little ginsenoside F(2) production from ginsenosides Gyp XVII, C-O, and C-Mc(1) was observed for the lengthy enzyme reaction caused by the side ability of the enzyme. PMID:21906640
Microbial transformation of ginsenoside-Rg₁ by Absidia coerulea and the reversal activity of the metabolites towards multi-drug resistant tumor cells.
Liu, Xin; Qiao, Lirui; Xie, Dan; Zhang, Yi; Zou, Jianhua; Chen, Xiaoguang; Dai, Jungui
Biotransformation of ginsenoside-Rg₁ (1) by the fungus Absidia coerulea AS 3.2462 yielded five metabolites (2-6). On the basis of spectroscopic data analyses, the metabolites were identified as ginsenoside-F₁ (2), 6α,12β-dihydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3), 3-oxo-20(S)-protopanaxatriol (4), 3-oxo-7β-hydroxy-20(S)-protopanaxatriol (5), and 3-oxo-7β,15α-dihydroxy-20(S)-protopanaxatriol (6), respectively. Among them, 5 and 6 are new compounds. These results indicated that Absidia coerulea AS 3.2462 could catalyze the specific C-3 dehydrogenation of derivatives of ginsenoside-Rg₁, as well as hydroxylation at the 7β and 15α positions. Metabolites 2, 4 and 5 exhibited moderate reversal activity towards A549/taxol MDR tumor cells in vitro. PMID:21946057
Effect of Fermented Red Ginseng Extract Enriched in Ginsenoside Rg3 on the Differentiation and Mineralization of Preosteoblastic MC3T3-E1 Cells.
Siddiqi, Muhammad Zubair; Siddiqi, Muhammad Hanif; Kim, Yeon-Ju; Jin, Yan; Huq, Md Amdadul; Yang, Deok-Chun
In this study, red ginseng extract (RGE) was converted into high-content minor ginsenosides by fermenting with Bgp1 enzymes at 37°C for 5 days. Compared to the RGE, the minor ginsenoside contents were increased in fermented red ginseng extract (FRGE). Moreover, the amount of minor ginsenosides such as Rh1 (11%) and Rg2 (16%) was slightly augmented, while the level of Rg3 (33%) was significantly increased after bioconversion. Furthermore, we also examined and compared the effect of RGE and FRGE on the differentiation and mineralization of preosteoblastic MC3T3-E1 cells. Similarly, the level of mRNA expression of intracellular alkaline phosphatase (ALP) activity, type-1 collagen (Col-I) was also increased. Based on the comparison, it is clear that the FRGE has improved effects on bone formation and differentiation of preosteoblastic MC3T3-E1 cells. PMID:25764149
Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus.
Kim, Jong-Hoon; Cho, Soo Yeun; Lee, Jun-Ho; Jeong, Sang Min; Yoon, In-Soo; Lee, Byung-Hwan; Lee, Joon-Hee; Pyo, Mi Kyung; Lee, Sang-Mok; Chung, Jun-Mo; Kim, Sunoh; Rhim, Hyewhon; Oh, Jae-Wook; Nah, Seung-Yeol
We previously demonstrated that ginsenoside Rg(3) (Rg(3)), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents and NMDA-induced neurotoxicity (Kim, S., Kim, T., Ahn, K., Park, W.K., Nah, S.Y., Rhim, H., 2004. Ginsenoside Rg(3) antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem. Biophys. Res. Commun. 323, 416-424). Accumulating evidence suggests that homocysteine (HC), a metabolite of methionine, exerts its excitotoxicity through NMDA receptor activation. In the present study, we examined the neuroprotective effects of Rg(3) on HC-induced hippocampal excitotoxicity in vitro and in vivo. Our in vitro studies using rat cultured hippocampal neurons revealed that Rg(3) treatment significantly and dose-dependently inhibited HC-induced hippocampal cell death, with an EC(50) value of 28.7+/-7.5 muM. Rg(3) treatment not only significantly reduced HC-induced DNA damage, but also dose-dependently attenuated HC-induced caspase-3 activity in vitro. Our in vivo studies revealed that intracerebroventricular (i.c.v.) pre-administration of Rg(3) significantly and dose-dependently reduced i.c.v. HC-induced hippocampal damage in rats. To examine the mechanisms underlying the in vitro and in vivo neuroprotective effects of Rg(3) against HC-induced hippocampal excitotoxicity, we examined the effect of Rg(3) on HC-induced intracellular Ca(2+) elevations in cultured hippocampal cells and found that Rg(3) treatment dose-dependently inhibited HC-induced intracellular Ca(2+) elevation, with an IC(50) value of 41.5+/-17.5 muM. In addition, Rg(3) treatment dose-dependently inhibited HC-induced currents in Xenopus oocytes expressing the NMDA receptor, with an IC(50) of 47.3+/-14.2 muM. These results collectively indicate that Rg(3)-induced neuroprotection against HC in rat hippocampus might be achieved via inhibition of HC-mediated NMDA receptor activation. PMID:17239831
Ginsenoside F2 possesses anti-obesity activity via binding with PPARγ and inhibiting adipocyte differentiation in the 3T3-L1 cell line.
Siraj, Fayeza Md; SathishKumar, Natarajan; Kim, Yeon Ju; Kim, Se Young; Yang, Deok Chun
Abstract Panax ginseng Meyer has been shown to be effective in mitigating various diseases. Protopanaxadiols (PPD) and protopanaxatriols (PPT), which are the main constituents of ginseng, have been shown to impact obesity. Therefore, we selected several important ginsenosides to perform our docking study and determine if they had binding affinity with the peroxisome proliferator activated receptor gamma (PPARγ), which is a major transcription factor in adipocytes. Among them, only a few ginsenosides demonstrated binding affinity with PPARγ. Other than ginsenoside F2 rest of them were previously reported by the researchers in experimental study in case of obesity cell line 3T3-L1 adipocyte. In few recent studies, it was reported that F2 has protective effects on malignant brain tumors as well as anti-cancer activity in breast cancer. Therefore, we felt it was important to focus on F2 when considering obesity. Our study focused on this ginsenoside and analyzed its impact on 3T3-L1 adipocytes. Following the molecular interaction studies, further experimental studies were carried out and demonstrated that ginsenoside F2 when treated with different doses reduces the level of lipid accumulated by the 3T3-L1 cell line during adipogenesis. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative real-time PCR results showed reduction in PPARγ and perilipin gene expression levels compared to that of differentiated adipocytes without any treatment. So considering the binding with a major adipocyte transcription factor and the performed experiments, we suggest that ginsenoside F2 may reduce obesity via the inhibition of adipogenesis in the 3T3-L1 cell line. PMID:24666293
Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.
Wang, Lei; Li, Xiankui; Song, Yi-Min; Wang, Bin; Zhang, Fu-Rui; Yang, Rui; Wang, Hua-Qi; Zhang, Guo-Jun
At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression. PMID:25738799
Ginsenoside Rb1 inhibits matrix metalloproteinase 13 through down-regulating Notch signaling pathway in osteoarthritis.
Wang, Wei; Zeng, Li; Wang, Ze-ming; Zhang, Sihan; Rong, Xiao-Feng; Li, Rong-Heng
Mounting evidence suggests that an excess of matrix metalloproteinase-13 (MMP-13) plays an important role in the breakdown of extracellular matrix in osteoarthritis (OA). Here, the effects of ginsenoside Rb1 (GRb1) on the expression of MMP-13 in IL-1β-induced SW 1353 chondrosarcoma cells and an experimental rat model of OA induced by anterior cruciate ligament transection (ACLT) were investigated. SW1353 chondrosarcoma cells were pretreated with or without GRb1 and Notch signaling pathway inhibitor, DAPT, then were stimulated with IL-1β. In rats, experimental OA was induced by ACLT. These rats then received intra-articular injections of vehicle, an inhibitor of γ-secretase, DAPT, and/or GRb1. Expression of MMP-13, collagen type II (CII), Notch1, and jagged 1 (JAG1) were verified by western blotting and immunohistochemistry. In addition, levels of MMP-13 mRNA were detected using quantitative real-time PCR. In histological analyses, treatment with DAPT reduced the number of cartilage lesions present and the expressions of MMP-13, CII, Notch1, and JAG1. In addition, treatment with GRb1 was associated with lower levels of Notch1 and JAG1 in both IL-1β-induced SW1353 chondrosarcoma cells and in the rat OA model. Furthermore, the suppressive effect of GRb1 on MMP-13 was greater than that exhibited by the signaling pathway inhibitor. In conclusion, GRb1 inhibits MMP-13 through down-regulating Notch signaling pathway in OA. PMID:26062798
Ginsenoside Rh2 inhibits hepatocellular carcinoma through β-catenin and autophagy
Yang, Zhiqing; Zhao, Tingting; Liu, Hongli; Zhang, Leida
Hepatocellular carcinoma (HCC) is the most common liver cancer, with a very poor prognosis. There is an urgent need for an effective therapy for HCC. Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancer, whereas its effects on HCC have not been examined. Here, we treated human HCC cells with different doses of GRh2, and found that GRh2 dose-dependently reduced HCC viability, in either CCK-8 assay or MTT assay. The effects of GRh2 on the cancer stem cells (CSCs)-like cells were determined by aldefluor flow cytometry and by tumor sphere formation, showing that GRh2 dose-dependently decreased the number of these CSCs-like cells in HCC. Autophagy-associated protein and β-catenin level were measured in GRh2-treated HCC cells by Western blot, showing that GRh2 increased autophagy and inhibited β-catenin signaling. Expression of short hairpin small interfering RNA (shRNA) for Atg7 in HCC cells completely abolished the effects of GRh2 on β-catenin and cell viability, while overexpression of β-catenin abolished the effects of GRh2 on autophagy and cell viability. Together, our data suggest that GRh2 may inhibit HCC cell growth, possibly through a coordinated autophagy and β-catenin signaling. PMID:26783250
Protective effects of ginsenoside Re on lipopolysaccharide-induced cardiac dysfunction in mice.
Chen, Rong-Chang; Wang, Jian; Yang, Longpo; Sun, Gui-Bo; Sun, Xiao-Bo
The impaired cardiac function caused by reduced myocardial contractility is a typical manifestation of sepsis/septic shock. Ginsenoside Re (GS-Re) is one of the most abundant ingredients of ginseng. This study was designed to investigate the protective effects of GS-Re on lipopolysaccharide (LPS)-induced septic cardiac dysfunction and inflammatory response in mice. Mice were intragastrically administered with GS-Re (15 mg kg(-1)) for 1 week before the LPS challenge (10 mg kg(-1), i.p.). Cardiac function was evaluated 6 h after LPS induction. GS-Re pretreatment significantly protected against LPS-induced cardiac dysfunction. GS-Re ameliorated the imbalance between iNOS and eNOS, and prevented NF-κB activation and subsequent myocardial inflammatory responses in endotoxemic mice. The effects of GS-Re were closely associated with estrogen receptors (ERs), phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling, and the mitogen-activated protein kinase signaling pathway, as characterized by the GS-Re-induced preservation of ERα, ERβ, and phospho-Akt and inhibition of phospho-ERK1/2, phospho-JNK, phospho-P38. However, GS-Re had no effect on LPS-induced activation of TLR-4. All these results showed that GS-Re pretreatment significantly attenuated LPS-induced cardiac dysfunction and inflammatory response. PMID:27074714
Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng
Baek, Kwang-Soo; Hong, Yong Deog; Kim, Yong; Sung, Nak Yoon; Yang, Sungjae; Lee, Kyoung Min; Park, Joo Yong; Park, Jun Seong; Rho, Ho Sik; Shin, Song Seok; Cho, Jae Youl
Background Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. Methods The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. Results AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. Conclusion Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy. PMID:26045689
Ginsenoside Rh2 induces ligand-independent Fas activation via lipid raft disruption
Yi, Jae-Sung; Choo, Hyo-Jung; Cho, Bong-Rae; Kim, Hwan-Myung; Kim, Yong-Nyun; Ham, Young-Mi; Ko, Young-Gyu
Lipid rafts are plasma membrane platforms mediating signal transduction pathways for cellular proliferation, differentiation and apoptosis. Here, we show that membrane fluidity was increased in HeLa cells following treatment with ginsenoside Rh2 (Rh2), as determined by cell staining with carboxy-laurdan (C-laurdan), a two-photon dye designed for measuring membrane hydrophobicity. In the presence of Rh2, caveolin-1 appeared in non-raft fractions after sucrose gradient ultracentrifugation. In addition, caveolin-1 and GM1, lipid raft landmarkers, were internalized within cells after exposure to Rh2, indicating that Rh2 might disrupt lipid rafts. Since cholesterol overloading, which fortifies lipid rafts, prevented an increase in Rh2-induced membrane fluidity, caveolin-1 internalization and apoptosis, lipid rafts appear to be essential for Rh2-induced apoptosis. Moreover, Rh2-induced Fas oligomerization was abolished following cholesterol overloading, and Rh2-induced apoptosis was inhibited following treatment with siRNA for Fas. This result suggests that Rh2 is a novel lipid raft disruptor leading to Fas oligomerization and apoptosis.
Use of ginsenoside Rg3-loaded electrospun PLGA fibrous membranes as wound cover induces healing and inhibits hypertrophic scar formation of the skin.
Sun, Xiaoming; Cheng, Liying; Zhu, Wankun; Hu, Changmin; Jin, Rong; Sun, Baoshan; Shi, Yaoming; Zhang, Yuguang; Cui, Wenguo
Prevention of hypertrophic scar formation of the skin requires a complex treatment process, which mainly includes promoting skin regeneration in an early stage while inhibiting hypertrophic formation in a later stage. Electrospinning PLGA with the three-dimensional micro/nano-fibrous structure and as drugs carrier, could be used as an excellent skin repair scaffold. However, it is difficult to combine the advantage of nanofibrous membranes and drug carriers to achieve early and late treatment. In this study, Ginsenoside-Rg3 (Rg3) loaded hydrophilic poly(D,L-lactide-co-glycolide) (PLGA) electrospun fibrous membranes coated with chitosan (CS) were fabricated by combining electrospinning and pressure-driven permeation (PDP) technology. The PDP method was able to significantly improve the hydrophilicity of electrospun fibrous membranes through surface coating of the hydrophilic fibers with CS, while maintaining the Rg3 releasing rate of PLGA electrospun fibrous membranes. Experimental wounds of animal covered with PDP treated fibrous membranes completely re-epithelialized and healed 3-4 days earlier than the wounds in control groups. Scar elevation index (SEI) measurements and histologic characteristics revealed that Rg3 significantly inhibited scar formation 28 days post-surgery. Moreover, RT-PCR assays and western blot analysis revealed that at day 28 after wound induction the expression of VEGF, mRNA and Collagen Type I in the scars treated with Rg3 was decreased compared to control groups. Taken together PLGA-Rg3/CS electrospun fibrous membranes induced repair of tissue damage in the early stage and inhibited scar formation in the late stage of wound healing. These dual-functional membranes present a combined therapeutic approach for inhibiting hypertrophic scars of the skin. PMID:24333554
Active compounds in Chinese herbs and medicinal animal products which promote blood circulation via inhibition of Na+, K+-ATPase.
Tzen, Jason Tc; Chen, Ronald Jy; Chung, Tse-Yu; Chen, Yi-Ching; Lin, Nan-Hei
The therapeutic effect of cardiac glycosides for congestive heart failure lies in their reversible inhibition on Na+, K+-ATPase located in human myocardium. Several steroid-like compounds containing a core structure similar to cardiac glycosides have been found in many Chinese herbs and medicinal animal products conventionally used to promote blood circulation. They are putatively responsible for the therapeutic effect of those medicinal products via the same mechanism of inhibiting Na+, K+-ATPase. Inhibitory potency on Na+, K+-ATPase by ginsenosides, one of the identified steroid-like compounds, is significantly affected by sugar attachment that might cause steric hindrance of their binding to Na+, K+-ATPase. Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, substantially inhibit Na+, K+-ATPase. However, their inhibitory potency is abolished when sugar moieties are linked to the C-6 or C-20 position of the steroid-like structure. In contrast, no appreciable contents of steroid-like compounds are found in danshen, a well-known Chinese herb traditionally regarded as an effective medicine promoting blood circulation. Instead, magnesium lithospermate B (MLB), the major soluble ingredient in danshen, is assumed to be responsible for the therapeutic effect by inhibiting Na+, K+-ATPase in a manner comparable to cardiac glycosides. Neuroprotective effects of cardiac glycosides, ginsenosides and MLB against ischemic stroke were accordingly observed in a cortical brain slice-based assay model. Whether the neuroprotection is also triggered by inhibition of Na+, K+-ATPase remains to be investigated. Molecular modeling suggests that cardiac glycosides, ginsenosides and MLB presumably bind to the same extracellular pocket of the Na+, K+-ATPase alpha subunit. PMID:20438664
Rescue of PINK1 protein null-specific mitochondrial complex IV deficits by ginsenoside Re activation of nitric oxide signaling.
Kim, Kyung-Hee; Song, Karen; Yoon, Seung-Hee; Shehzad, Omer; Kim, Yeong-Shik; Son, Jin H
PINK1, linked to familial Parkinson's disease, is known to affect mitochondrial function. Here we identified a novel regulatory role of PINK1 in the maintenance of complex IV activity and characterized a novel mechanism by which NO signaling restored complex IV deficiency in PINK1 null dopaminergic neuronal cells. In PINK1 null cells, levels of specific chaperones, including Hsp60, leucine-rich pentatricopeptide repeat-containing (LRPPRC), and Hsp90, were severely decreased. LRPPRC and Hsp90 were found to act upstream of Hsp60 to regulate complex IV activity. Specifically, knockdown of Hsp60 resulted in a decrease in complex IV activity, whereas antagonistic inhibition of Hsp90 by 17-(allylamino) geldanamycin decreased both Hsp60 and complex IV activity. In contrast, overexpression of the PINK1-interacting factor LRPPRC augmented complex IV activity by up-regulating Hsp60. A similar recovery of complex IV activity was also induced by coexpression of Hsp90 and Hsp60. Drug screening identified ginsenoside Re as a compound capable of reversing the deficit in complex IV activity in PINK1 null cells through specific increases of LRPPRC, Hsp90, and Hsp60 levels. The pharmacological effects of ginsenoside Re could be reversed by treatment of the pan-NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) and could also be reproduced by low-level NO treatment. These results suggest that PINK1 regulates complex IV activity via interactions with upstream regulators of Hsp60, such as LRPPRC and Hsp90. Furthermore, they demonstrate that treatment with ginsenoside Re enhances functioning of the defective PINK1-Hsp90/LRPPRC-Hsp60-complex IV signaling axis in PINK1 null neurons by restoring NO levels, providing potential for new therapeutics targeting mitochondrial dysfunction in Parkinson's disease. PMID:23144451
Effects of Natural Bioactive Products on the Growth and Ginsenoside Contents of Panax ginseng Cultured in an Aeroponic System
Kim, Geum-Soog; Lee, Seung-Eun; Noh, Hyung-Jun; Kwon, Hyuck; Lee, Sung-Woo; Kim, Seung-Yu; Kim, Yong-Bum
This study was conducted to evaluate the effects of natural bioactive products such as Manda enzyme (T1), Yangmyeongwon (T2), effective microorganisms (T3), and Kelpak (T4) on the growth and ginsenoside contents of Panax ginseng cultured in an aeroponic system using a two-layer vertical type of nutrient bath under natural light conditions. The growth of ginseng plants showed specific characteristics according to the positions in which they were cultured due to the difference of light transmittance and temperature in the upper and lower layers during aeroponic culture in a two-layer vertical type of system. The growth of the aerial part of the leaves and stems of ginseng plants cultured in the lower layer (4,000 to 6,000 lx, 23℃ to 26℃) of the nutrient bath was observed to be superior to that of the ginseng plants cultured in the upper layer (12,000 to 15,000 lx, 25℃ to 28℃). The leaf area was significantly larger in the treatment of T2 and T4 (46.70 cm2) than with other treatments. Conversely, the values of the root weight and root diameter were higher in ginseng plants cultured in the upper layer of the nutrient bath. The root weight was significantly heavier in the treatment of T4 (6.46 g) and T3 (6.26 g) than with other treatments. The total ginsenoside content in the leaves and roots was highest in the ginseng plants cultured by the treatment of T1, at 16.20%, while the total ginsenoside content obtained by other treatments decreased in the order of T4, T5 (control), T2, and T3, at 13.21%, 12.30%, 14.84%, and 14.86%, respectively. The total ginsenoside content of the ginseng leaves was found to be significantly higher in the treatment of T1 in the lower layer of the nutrient bath, at 15.30%, while the content of the ginseng roots in the treatments of T3 and T4, at 1.27% and 1.23%, respectively, was significantly higher than in other treatments in the upper layer of the nutrient bath. PMID:23717147
Efficient silkworm expression of single-chain variable fragment antibody against ginsenoside Re using Bombyx mori nucleopolyhedrovirus bacmid DNA system and its application in enzyme-linked immunosorbent assay for quality control of total ginsenosides.
Sakamoto, Seiichi; Pongkitwitoon, Benyakan; Nakamura, Seiko; Maenaka, Katsumi; Tanaka, Hiroyuki; Morimoto, Satoshi
A single-chain variable fragment (scFv) antibody against ginsenoside Re (G-Re) have been successfully expressed in the silkworm larvae using Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA system. The baculovirus donor vector for expression of scFv against G-Re (GRe-scFv) was constructed to contain honeybee melittin signal sequence to accelerate secretion of the recombinant GRe-scFv into the haemolymph of silkworm larvae. Functional recombinant GRe-scFv was purified by cation exchange chromatography followed by immobilized metal ion affinity chromatography. The yield of purified GRe-scFv was 6.5 mg per 13 silkworm larvae, which is equivalent to 650 mg/l of the haemolymph, exhibiting extremely higher yield than that expressed in Escherichia coli (1.7 mg/l of culture medium). It was revealed from characterization that GRe-scFv retained similar characteristic of the parental monoclonal antibody (MAb) against G-Re (MAb-4G10), making it possible to develop indirect competitive enzyme-linked immunosorbent assay (icELISA) for quality control of total ginsenosides in various ginsengs. The detectable range for calibration of G-Re by developed icELISA shows 0.05-10 microg/ml. These results clearly suggested that the silkworm expression system is quite useful for the expression of functional scFv that frequently required time- and cost-consuming re-folding when it expressed in E. coli. PMID:20592135
Elicitors' influenced differential ginsenoside production and exudation into medium with concurrent Rg3/Rh2 panaxadiol induction in Panax quinquefolius cell suspensions.
Biswas, Tanya; Kalra, Alok; Mathur, A K; Lal, R K; Singh, Manju; Mathur, Archana
Cobalt nitrate, nickel sulphate, hydrogen peroxide, sodium nitroprusside, and culture filtrates of Pseudomonas monteili, Bacillus circularans, Trichoderma atroviridae, and Trichoderma harzianum were tested to elicit ginsenoside production in a cell suspension line of Panax quinquefolius. Abiotic elicitors preferentially increased panaxadiols whereas biotic elicitors upregulated the panaxatriol synthesis. Cobalt nitrate (50 μM) increased total ginsenosides content by twofold (54.3 mg/L) within 5 days. It also induced the Rc synthesis that was absent in the control cultures. Elicitation with P. monteili (2.5 % v/v, 5 days) also supported 2.4-fold enhancement in saponin yield. Elicitation by T. atroviridae or hydrogen peroxide induced the synthesis of Rg3 and Rh2 that are absent in ginseng roots. The highest ginsenosides productivity (3.2-fold of control) was noticed in cells exposed to 1.25 % v/v dose of T. atroviridae for 5 days. Treating cells with T. harzianum for 15 days afforded maximum synthesis and leaching (8.1 mg/L) of ginsenoside Rh1. PMID:26795963
Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells
Park, Jun Yeon; Choi, Pilju; Lee, Dahae; Kim, Taejung; Jung, Eun Bee; Hwang, Buyng-Su; Kang, Ki Sung; Ham, Jungyeob
Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S)-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S)-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S)-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R)-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S)-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S)-Rg3. PMID:27051448
UPLC-Q-TOF-MS/MS Analysis for Steaming Times-dependent Profiling of Steamed Panax quinquefolius and Its Ginsenosides Transformations Induced by Repetitious Steaming
Sun, Bai-Shen; Xu, Ming-Yang; Li, Zheng; Wang, Yi-Bo; Sung, Chang-Keun
The metabolic profiles of Panax quinquefolius and its associated therapeutic values are critically affected by the repetitious steaming times. The times-dependent steaming effect of P. quinquefolius is not well-characterized and there is also no official guideline on its times of steaming. In this paper, a UPLC-Q-TOF-MS/MS method was developed for the qualitative profiling of multi-parametric metabolic changes of raw P. quinquefolius during the repetitious steaming process. Our method was successful in discriminating the differentially multi-steamed herbs. Meantime, the repetitious steaming-inducing chemical transformations in the preparation of black American ginseng (American ginseng that was subjected to 9 cycles of steaming treatment) were evaluated by this UPLC-Q-TOF-MS/MS based chemical profiling method. Under the optimized UPLC-Q-TOF-MS/MS conditions, 29 major ginsenosides were unambiguously identified and/or tentatively assigned in both raw and multi-steamed P. quinquefolius within 19 min, among them 18 ginsenosides were detected to be newly generated during the preparatory process of black American ginseng. The mechanisms involved were further deduced to be hydrolysis, dehydration, decarboxylation and addition reactions of the original ginsenosides in raw P. quinquefolius through analyzing mimic 9 cycles of steaming extracts of 14 pure reference ginsenosides. Our novel steaming times-dependent metabolic profiling approach represents the paradigm shift in the global quality control of multi-steamed P. quinquefolius products. PMID:23717129
Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells.
Park, Jun Yeon; Choi, Pilju; Lee, Dahae; Kim, Taejung; Jung, Eun Bee; Hwang, Buyng-Su; Kang, Ki Sung; Ham, Jungyeob
Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S)-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S)-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S)-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R)-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S)-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S)-Rg3. PMID:27051448
Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype
Ren, Kaixi; Jin, Chao; Ma, Pengfei; Ren, Qinyou; Jia, Zhansheng; Zhu, Daocheng
Background Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10–100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with CD11b+, iNOS+/interleukin-12/tumor necrosis factor-α labeling. For the in vitro study, GSRd (10–100 μg/mL) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin–eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-α. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization. PMID:27158241
Quantitative determination of ginsenoside Rh2 in rat biosamples by liquid chromatography electrospray ionization mass spectrometry.
Gu, Yi; Wang, Guang-Ji; Sun, Jian-Guo; Jia, Yuan-Wei; Xie, Hai-Tang; Wang, Wei
Ginsenoside Rh2 is a "hot" natural compound with great potential as a new anti-cancer drug based on abundant pharmacological experiments. However, no systemic pharmacokinetic study of Rh2 was reported because current analysis methods could not fully meet the requirements. Thus, we developed a simple LC/MS method with highly improved sensitivities for the determination of Rh2 in rat plasma, bile, urine, feces and most tissues. The tissues and feces were firstly homogenized mechanically using buffer and methanol as the media, respectively. Plasma, bile, urine and tissue homogenates were extracted with diethyl ether for sample preparation. Feces homogenates were directly deproteinized with acetonitrile. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer), with an ODS column (150 mm x 2.0-mm i.d., 5 microm) plus a C18 guard column for separation and ammonium chloride (500 micromol) as mobile phase additive. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M + Cl]- of Rh2 at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in selective ion monitoring mode of negative ions. The method was validated to be accurate, precise and rugged with good linearity in all matrices, according to the FDA guidelines. The lower limits of quantitation in rat plasma, urine and feces were 0.2, 0.2 and 20 ng/mL respectively. Stability studies were also performed, indicating that there were no stability-related problems in the analytical procedure of Rh2. The proposed method was successfully applied to the preclinical pharmacokinetic research of Rh2 in rats, including plasma kinetics, tissue distribution and excretion studies. PMID:17082877
Ginsenoside Rh2 alleviates tumor-associated depression in a mouse model of colorectal carcinoma.
Wang, Jia; Chen, Yueming; Dai, Chunxiao; Shang, Yushan; Xie, Jian
Previous studies reported remarkable high incidence of depression in cancer patients compared with the general population. Colorectal carcinoma (CRC) is one of the most frequent malignancies worldwide and has been found to be one of the malignancies with the highest incidence of patient depression. Thus, strategies that may alleviate CRC-associated depression may significantly improve the patients' life quality and outcome of the therapy. Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on various diseases. However, whether it may also play a potential role in alleviating tumor-associated depression in CRC patients is unknown. Here, we studied the role of GRh2 in the control of depression in CRC using a mouse model. CRC was induced in mice through orthotopic implantation. GRh2 or control vehicle was then given to the mice twice per week for 4 weeks, after which the mice were subjected to a forced swim test (FST), a tail suspension test (TST) and a sucrose intake test (SIT). We found that the mice that received GRh2 treatment significantly improved their behaviors in all FST, TST and SIT tests, seemingly through decreases in the depression-associated cytokines, interleukin 6 (IL-6), IL-18 and tumor necrosis factor-alpha. Moreover, GRh2 significantly increased survival time of the CRC-mice. Together, our data suggest that GRh2 may alleviate tumor-associated depression in mice carrying CRC and highlight GRh2 treatment as a potential beneficial therapy for CRC-associated depression in patients. PMID:27347326
Electrospun Poly(L-Lactide) Fiber with Ginsenoside Rg3 for Inhibiting Scar Hyperplasia of Skin
Hu, Changmin; Li, Haiyan; Zhang, Yuguang; Chang, Jiang
Hypertrophic scarring (HS) has been considered as a great concern for patients and a challenging problem for clinicians as it can be cosmetically disfiguring and functionally debilitating. In this study, Ginsenoside Rg3/Poly(l-lactide) (G-Rg3/PLLA) electrospun fibrous scaffolds covering on the full-thickness skin excisions location was designed to suppress the hypertrophic scar formation in vivo. SEM and XRD results indicated that the crystal G-Rg3 carried in PLLA electrospun fibers was in amorphous state, which facilitates the solubility of G-Rg3 in the PLLA electrospun fibrous scaffolds, and solubility of G-Rg3 in PBS is increased from 3.2 µg/ml for pure G-Rg3 powders to 19.4 µg/ml for incorporated in PLLA-10% fibers. The released G-Rg3 content in the physiological medium could be further altered from 324 to 3445 µg in a 40-day release period by adjusting the G-Rg3 incorporation amount in PLLA electrospun fibers. In vitro results demonstrated that electrospun G-Rg3/PLLA fibrous scaffold could significantly inhibit fibroblast cell growth and proliferation. In vivo results confirmed that the G-Rg3/PLLA electrospun fibrous scaffold showed significant improvements in terms of dermis layer thickness, fibroblast proliferation, collagen fibers and microvessels, revealing that the incorporation of the G-Rg3 in the fibers prevented the HS formation. The above results demonstrate the potential use of G-Rg3/PLLA electrospun fibrous scaffolds to rapidly minimize fibroblast growth and restore the structural and functional properties of wounded skin for patients with deep trauma, severe burn injury, and surgical incision. PMID:23874757
Ginsenoside Rh2 alleviates tumor-associated depression in a mouse model of colorectal carcinoma
Wang, Jia; Chen, Yueming; Dai, Chunxiao; Shang, Yushan; Xie, Jian
Previous studies reported remarkable high incidence of depression in cancer patients compared with the general population. Colorectal carcinoma (CRC) is one of the most frequent malignancies worldwide and has been found to be one of the malignancies with the highest incidence of patient depression. Thus, strategies that may alleviate CRC-associated depression may significantly improve the patients' life quality and outcome of the therapy. Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on various diseases. However, whether it may also play a potential role in alleviating tumor-associated depression in CRC patients is unknown. Here, we studied the role of GRh2 in the control of depression in CRC using a mouse model. CRC was induced in mice through orthotopic implantation. GRh2 or control vehicle was then given to the mice twice per week for 4 weeks, after which the mice were subjected to a forced swim test (FST), a tail suspension test (TST) and a sucrose intake test (SIT). We found that the mice that received GRh2 treatment significantly improved their behaviors in all FST, TST and SIT tests, seemingly through decreases in the depression-associated cytokines, interleukin 6 (IL-6), IL-18 and tumor necrosis factor-alpha. Moreover, GRh2 significantly increased survival time of the CRC-mice. Together, our data suggest that GRh2 may alleviate tumor-associated depression in mice carrying CRC and highlight GRh2 treatment as a potential beneficial therapy for CRC-associated depression in patients. PMID:27347326
Ginsenoside Rd Is Efficacious Against Acute Ischemic Stroke by Suppressing Microglial Proteasome-Mediated Inflammation.
Zhang, Guangyun; Xia, Feng; Zhang, Yunxia; Zhang, Xiao; Cao, Yuhong; Wang, Ling; Liu, Xuedong; Zhao, Gang; Shi, Ming
A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic stroke. In this study, we conducted a pooled analysis of the data from 199 patients with acute ischemic stroke in the first trial and 390 in the second to reanalyze the efficacy and safety of Rd. Moreover, animal stroke models were carried out to explore the possible molecular mechanisms underlying Rd neuroprotection. The pooled analysis showed that compared with placebo group, Rd could improve patients' disability as assessed by modified Rankin Scale (mRS) score on day 90 post-stroke and reduce neurologic deficits on day 15 or day 90 post-stroke as assessed by NIH Stroke Scale (NIHSS) and Barthel Index (BI) scores. For neuroprotective mechanisms, administration of Rd 4 h after stroke could inhibit ischemia-induced microglial activation, decrease the expression levels of various proinflammatory cytokines, and suppress nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation. An in vitro proteasome activity assay revealed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was showed to have less side effects than glucocorticoid. Therefore, our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation. PMID:26081140
Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training
Sun, Mengwei; Huang, Chenglin; Wang, Cheng; Zheng, Jianheng; Zhang, Peng; Xu, Yangshu; Chen, Hong; Shen, Weili
Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissue of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria.
A chimera of green fluorescent protein with single chain variable fragment antibody against ginsenosides for fluorescence-linked immunosorbent assay.
Sakamoto, Seiichi; Tanizaki, Yusuke; Pongkitwitoon, Benyakan; Tanaka, Hiroyuki; Morimoto, Satoshi
A chimera of green fluorescent protein extracted from Aequorea coerulescens (AcGFP), a mutant that has been codon optimized for mammalian expression, with single-chain variable fragment (scFv) antibody against ginsenoside Re (GRe-scFv), named fluobody, has been successfully expressed in Escherichia coli (E. coli) to develop simple, speedy, and sensitive fluorescence-linked immunosorbent assay (FLISA). Two chimera proteins were constructed to contain GRe-scFv at the C-terminus of AcGFP (C-fluobody) and at the N-terminus of AcGFP (N-fluobody). These fluobodies were then purified by ion metal affinity chromatography and refolded by stepwise dialysis. The characterization of both fluobodies revealed that C-fluobody was found to be appropriate probe for FLISA as compare with N-fluobody. Furthermore, improvement of limit of detection (LOD) was observed in FLISA using C-fluobody (10 ng/mL) due to its strong fluorescence intensity of AcGFP compared with conventional enzyme-linked immunosorbent assay (ELISA) using parental monoclonal antibody against ginsenoside Re (G-Re), MAb-4G10 (100 ng/mL). Since some steps required in ELISA can be avoided in this present FLISA, speedy and sensitive immunoassay also could be performed using fluobody instead of monoclonal antibody and scFv. PMID:21277981
Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions.
Wang, Wei-Nan; Yan, Bing-Xiong; Xu, Wen-Di; Qiu, Ye; Guo, Yun-Long; Qiu, Zhi-Dong
Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO₄ without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C-50 °C. Then, a biotransformation pathway of Rb1→Rd→F2→CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes. PMID:26512632
An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid.
Zhao, Chunyan; Sun, Runbin; Cao, Bei; Gu, Shenghua; Zhao, Jieyu; Liu, Linsheng; Wang, Xinwen; Zha, Weibin; Yu, Xiaoyi; Xiao, Wenjing; Mao, Yong; Ge, Chun; Ju, Jiaqi; Aa, Lixiang; Fei, Fei; Ding, Yi; Aa, Jiye; Wang, Guangji
For orally administered drugs, the metabolism of a drug by the gut flora plays an important role in the bioavailability, activation and disposition of the drug in vivo. However, no in vitro system is currently available to evaluate the metabolism of a drug by the gut flora before the drug is absorbed into the body. This paper presents an in vitro metabolic system in an anaerobic environment that could be used to evaluate the metabolism of an endogenous compound, cholic acid, and a xenobiotic compound, ginsenoside Rg3. We showed that the proliferation of the anaerobic bacteria of the gut content of hamsters produced a similar composition of gut flora in a culture medium for yeast to that in vivo. Incubation of ginsenoside Rg3 and cholic acid in the anaerobic in vitro system efficiently produced the metabolites Rh2 and deoxycholic acid, respectively, similar to those seen in the gut content in vivo. In comparison with in vivo analysis, this anaerobic in vitro metabolic system is convenient, reproducible, economic and animal saving, and can easily be applied to assess the transformation and disposition of a drug before it enters into the circulatory system. PMID:23749587
Production of Ginsenoside F2 by Using Lactococcus lactis with Enhanced Expression of β-Glucosidase Gene from Paenibacillus mucilaginosus.
Li, Ling; Shin, So-Yeon; Lee, Soo Jin; Moon, Jin Seok; Im, Wan Taek; Han, Nam Soo
This study aimed to produce a pharmacologically active minor ginsenoside F2 from the major ginsenosides Rb1 and Rd by using a recombinant Lactococcus lactis strain expressing a heterologous β-glucosidase gene. The nucleotide sequence of the gene (BglPm) was derived from Paenibacillus mucilaginosus and synthesized after codon optimization, and the two genes (unoptimized and optimized) were expressed in L. lactis NZ9000. Codon optimization resulted in reduction of unfavorable codons by 50% and a considerable increase in the expression levels (total activities) of β-glucosidases (0.002 unit/mL, unoptimized; 0.022 unit/mL, optimized). The molecular weight of the enzyme was 52 kDa, and the purified forms of the enzymes could successfully convert Rb1 and Rd into F2. The permeabilized L. lactis expressing BglPm resulted in a high conversion yield (74%) of F2 from the ginseng extract. Utilization of this microbial cell to produce F2 may provide an alternative method to increase the health benefits of Panax ginseng. PMID:26494255
Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharide-stimulated macrophages.
Jeong, Jin-Ju; Van Le, Thi Hong; Lee, Sang-Yun; Eun, Su-Hyeon; Nguyen, Minh Duc; Park, Jeong Hill; Kim, Dong-Hyun
Panax vietnamensis Ha et Grushv., with its main constituents vina-ginsenoside R2 (VR2) and majonoside R2 (MR2), is used in traditional folk medicine in the hill tribes of Vietnam for anti-fatigue, anti-inflammatory, and life-saving purposes. In a preliminary study, VR2 and MR2 were shown to be metabolized to pseudoginsenoside RT4 (PRT4) and ocotillol by human gut microbiota. Therefore, we measured the anti-inflammatory effects of VR2, MR2, and their metabolites in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Among these ginsenosides, only VR2 exhibited cytotoxicity against peritoneal macrophages. MR2, PRT4, and ocotillol inhibited LPS-stimulated transcription factor (NF)-κB activation, and expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL)-1. However, these ginsenosides did not inhibit peptidoglycan-induced NF-κB activation in the macrophages. These three ginsenosides also inhibited LPS-stimulated cyclooxygenase-2 and inducible NO synthase expression, and phosphorylation of NF-κB signal molecules IL-1 receptor-associated kinase 1 and tumor growth factor-β-activated kinase 1 in peritoneal macrophages. Treatment with either PRT4 or ocotillol inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, as observed by flow cytometry. They also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages, both with and without transfected MyD88 siRNA. Among the tested ginsenosides, ocotillol exhibited the strongest inhibitory effect on inflammation in LPS-stimulated macrophages via the NF-κB signaling pathway. Based on these findings, orally administered VR2 and MR2 of P. vietnamensis may be metabolized to ocotillol via PRT4, and the metabolites, particularly ocotillol, may inhibit inflammation by inhibiting the binding of LPS to TLR4 on macrophages. PMID:26256699
Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.
Nam, Yunsung; Wie, Myung Bok; Shin, Eun-Joo; Nguyen, Thuy-Ty Lan; Nah, Seung-Yeol; Ko, Sung Kwon; Jeong, Ji Hoon; Jang, Choon-Gon; Kim, Hyoung-Chun
Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKCδ and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH-SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca(2+)), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase-3 and poly(ADP-ribose)polymerase-1, nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH-SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells. PMID:25523949
Identification of ginsenoside interaction sites in 5-HT3A receptors.
Lee, Byung-Hwan; Lee, Jun-Ho; Lee, Sang-Mok; Jeong, Sang Min; Yoon, In-Soo; Lee, Joon-Hee; Choi, Sun-Hye; Pyo, Mi Kyung; Rhim, Hyewhon; Kim, Hyoung-Chun; Jang, Choon-Gon; Lee, Byoung-Cheol; Park, Chul-Seung; Nah, Seung-Yeol
We previously demonstrated that 20(S)-ginsenoside Rg(3) (Rg(3)), one of the active components of Panax ginseng, non-competitively inhibits 5-HT(3A) receptor channel activity on extracellular side of the cell. Here, we sought to elucidate the molecular mechanisms underlying Rg(3)-induced 5-HT(3A) receptor regulation. We used the two-microelectrode voltage-clamp technique to investigate the effect of Rg(3) on 5-HT-mediated ion currents (I(5-HT)) in Xenopus oocytes expressing wild-type or 5-HT(3A) receptors harboring mutations in the gating pore region of transmembrane domain 2 (TM2). In oocytes expressing wild-type 5-HT(3A) receptors, Rg(3) dose-dependently inhibited peak I(5-HT) with an IC(50) of 27.6+/-4.3microM. Mutations V291A, F292A, and I295A in TM2 greatly attenuated or abolished the Rg(3)-induced inhibition of peak I(5-HT). Mutation V291A but not F292A and I295A induced constitutively active ion currents with decrease of current decay rate. Rg(3) accelerated the rate of current decay with dose-dependent manner in the presence of 5-HT. Rg(3) and TMB-8, an open channel blocker, dose-dependently inhibited constitutively active ion currents. The IC(50) values of constitutively active ion currents in V291A mutant receptor were 72.4+/-23.1 and 6.5+/-0.7microM for Rg(3) and TMB-8, respectively. Diltiazem did not prevent Rg(3)-induced inhibition of constitutively active ion currents in occlusion experiments. These results indicate that Rg(3) inhibits 5-HT(3A) receptor channel activity through interactions with residues V291, F292, and I295 in the channel gating region of TM2 and further demonstrate that Rg(3) regulates 5-HT(3A) receptor channel activity in the open state at different site(s) from those of TMB-8 and diltiazem. PMID:17257631
20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginsenoside Rb1, enhances the production of hyaluronic acid through the activation of ERK and Akt mediated by Src tyrosin kinase in human keratinocytes.
Lim, Tae-Gyu; Jeon, Ae Ji; Yoon, Ji Hye; Song, Dasom; Kim, Jong-Eun; Kwon, Jung Yeon; Kim, Jong Rhan; Kang, Nam Joo; Park, Jun-Seong; Yeom, Myeong Hun; Oh, Deok-Kun; Lim, Yoongho; Lee, Charles C; Lee, Chang Yong; Lee, Ki Won
The aim of the present study was to determine the mechanisms through which 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (20GPPD) promotes the production of hyaluronic acid (HA) in human keratinocytes. 20GPPD is the primary bioactive metabolite of Rb1, a major ginsenoside found in ginseng (Panax ginseng). We sought to elucidate the underlying mechanisms behind the 20GPPD-induced production of HA. We found that 20GPPD induced an increase in HA production by elevating hyaluronan synthase 2 (HAS2) expression in human keratinocytes. The phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was also enhanced by 20GPPD in a dose-dependent manner. The pharmacological inhibition of ERK (using U0126) or Akt (using LY294002) suppressed the 20GPPD-induced expression of HAS2, whereas treatment with an epidermal growth factor receptor (EGFR) inhibitor (AG1478) or an intracellular Ca2+ chelator (BAPTA/AM) did not exert any observable effects. The increased Src phosphorylation was also confirmed following treatment with 20GPPD in the human keratinocytes. Following pre-treatment with the Src inhibitor, PP2, both HA production and HAS2 expression were attenuated. Furthermore, the 20GPPD-enhanced ERK and Akt signaling decreased following treatment with PP2. Taken together, our results suggest that Src kinase plays a critical role in the 20GPPD-induced production of HA by acting as an upstream modulator of ERK and Akt activity in human keratinocytes. PMID:25738334
Korean red ginseng saponin fraction rich in ginsenoside-Rb1, Rc and Rb2 attenuates the severity of mouse collagen-induced arthritis.
Endale, Mehari; Im, Eun Ju; Lee, Joo Young; Kim, Sung Dae; Yayeh, Taddesse; Song, Yong-Bum; Kwak, Yi-Seong; Kim, Chaekyun; Kim, Seung-Hyung; Roh, Seong-Soo; Cho, Jae Youl; Rhee, Man Hee
Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3(+)/CD69(+), CD4(+)/CD25(+), CD8(+) T-cell, CD19(+), B220/CD23(+) B-cell, MHCII(+)/CD11c(+), and Gr-1(+)/CD11b(+) cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice. PMID:24833816
A Distinctive Pattern of Beauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells.
Gum, Sang Il; Rahman, Md Khalilur; Won, Jong Soon; Cho, Min Kyung
Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The β-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use. PMID:26609787
Tartaric acid induced conversion of protopanaxadiol to ginsenosides Rg3 and Rg5 and their in situ recoveries by integrated expanded bed adsorption chromatography.
Huang, Dan; Li, Yang; Zhang, Min; Ruan, Shengli; Zhang, Hongyang; Wang, Yuerong; Hu, Ping
Panax ginseng has been applied in traditional Chinese medicine for over 2000 years. It is still one of the most popular herbs in recent decades. The prescribed ginseng-containing medicines consist of protopanaxadiol and protopanaxatriol ginsenosides, which are the major constituents of the herb. Minor ginsenosides at low levels in the herb, such as Rg3 and Rg5 , have attracted more rising attention than the major ones. The existing approaches to prepare Rg3 and Rg5 usually rely on either steamed red ginseng as the source or chemical/enzymatic conversion of protopanaxadiol to the targets. It is still highly desirable to effectively achieve such minor components. In this paper, a method integrated extraction of protopanaxadiol and conversion of it to Rg3 and Rg5 has been proposed. Protopanaxadiol was extracted and simultaneously converted to Rg3 and Rg5 by d,l-tartaric acid. The targets were absorbed by resins on expanded bed adsorption chromatography and were then separated from other ginsenosides in different stages. Compared with conventional methods, the developed process has advantages in shortening time consumption and improving the conversion ratio of protopanaxadiol, which is promising in directly achieving Rg3 and Rg5 from P. ginseng. PMID:27288199
20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro.
Yang, Rui; Chen, Daozhen; Li, Mengfei; Miao, Fengqin; Liu, Peidang; Tang, Qiusha
20(s)-ginsenoside Rg3 is extracted from traditional Chinese medicine, red ginseng. However, due to its poor aqueous solubility and low oral bioavailability, the use of 20(s)-Rg3 is limited. This study aimed to explore a method of preparing nano-sized 20(s)-ginsenoside Rg3 particle named 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres (20(s)-Rg3/HSAMNP) to change dosage form to improve its aqueous solubility and bioavailability. 20(s)-Rg3/HSAMNP were prepared by the desolvation-crosslinking method. The character of 20(s)-Rg3/HSAMNP was detected. An antiproliferative effect and cell apoptosis rates of 20(s)-Rg3/HSAMNP on human cervical cancer cells were determined by the MTT assay and flow cytometry, respectively. TEM analysis showed that 20(s)-Rg3/HSAMNP were approximately spherical and uniform in size. Thermodynamic testing showed that the corresponding magnetic fluid of a specific concentration rosed to a steady temperature of 42-65○C. Iron content was approximately 3 mg/mL. Drug encapsulation efficiency was approximately 70%. The potential of 20(s)-Rg3/HSAMNP combined with magnetic hyperthermia therapy to inhibit cell growth and induce apoptosis was much more prominent than that of the other groups. A new dosage form of 20(s)-Rg3 was prepared, which effectively induced apoptosis in HeLa cervical cancer cells in vitro when combined with hyperthermia. PMID:25226895
A new validated analytical method for the quality control of red ginseng products
Kim, Il-Woung; Cha, Kyu-Min; Wee, Jae Joon; Ye, Michael B.; Kim, Si-Kwan
The main active components of Panax ginseng are ginsenosides. Ginsenoside Rb1 and Rg1 are accepted as marker substances for quality control worldwide. The analytical methods currently used to detect these two compounds unfairly penalize steamed and dried (red) P. ginseng preparations, because it has a lower content of those ginsenosides than white ginseng. To manufacture red ginseng products from fresh ginseng, the ginseng roots are exposed to high temperatures for many hours. This heating process converts the naturally occurring ginsenoside Rb1 and Rg1 into artifact ginsenosides such as ginsenoside Rg3, Rg5, Rh1, and Rh2, among others. This study highlights the absurdity of the current analytical practice by investigating the time-dependent changes in the crude saponin and the major natural and artifact ginsenosides contents during simmering. The results lead us to recommend (20S)- and (20R)-ginsenoside Rg3 as new reference materials to complement the current P. ginseng preparation reference materials ginsenoside Rb1 and Rg1. An attempt has also been made to establish validated qualitative and quantitative analytical procedures for these four compounds that meet International Conference of Harmonization (ICH) guidelines for specificity, linearity, range, accuracy, precision, detection limit, quantitation limit, robustness and system suitability. Based on these results, we suggest a validated analytical procedure which conforms to ICH guidelines and equally values the contents of ginsenosides in white and red ginseng preparations. PMID:24235862
Ionic liquid and aqueous two-phase extraction based on salting-out coupled with high-performance liquid chromatography for the determination of seven rare ginsenosides in Xue-Sai-Tong injection.
Li, Lan-Jie; Jin, Yong-Ri; Wang, Xiao-Zhong; Liu, Ying; Wu, Qian; Shi, Xiao-Lei; Li, Xu-Wen
A method of ionic liquid salt aqueous two-phase extraction coupled with high-performance liquid chromatography has been developed for the analysis of seven rare ginsenosides including Rg6 , F4 , 20(S)-Rg3 , 20(R)-Rg3 , Rk3 , Rk1 , and Rg5 in Xue-Sai-Tong injection. The injection was mixed with ionic liquid 1-butyl-3-methylimidazolium bromide aqueous solution, and a mixture was obtained. With the addition of sodium dodecyl sulfate and dipotassium phosphate into the mixture, the aqueous two-phase mixture was formed after ultrasonic treatment and centrifuged. Rare ginsenosides were extracted into the upper phase. To obtain a high extraction factors, various influences were considered systematically, such as the volume of ionic liquid, the category and amount of salts, the amount of sodium dodecyl sulfate, the pH value of system, and the time of ultrasonic treatment. Under the optimal condition, rare ginsenosides in Xue-Sai-Tong injection were enriched and detected, the recoveries of seven rare ginsenosides ranged from 90.05 to 112.55%, while relative standard deviations were lower than 2.50%. The developed method was reliable, rapid and sensitive for the determination of seven rare ginsenosides in the injections. PMID:26081987
Esterification of Ginsenoside Rh2 Enhanced Its Cellular Uptake and Antitumor Activity in Human HepG2 Cells.
Chen, Fang; Deng, Ze-Yuan; Zhang, Bing; Xiong, Zeng-Xing; Zheng, Shi-Lian; Tan, Chao-Li; Hu, Jiang-Ning
Our previous research had indicated that the octyl ester derivative of ginsenoside Rh2 (Rh2-O) might have a higher bioavailability than Rh2 in the Caco-2 cell line. The aim of this study was to investigate the cellular uptake and antitumor effects of Rh2-O in human HepG2 cells as well as its underlying mechanism compared with Rh2. Results showed that Rh2-O exhibited a higher cellular uptake (63.24%) than Rh2 (36.76%) when incubated with HepG2 cells for 24 h. Rh2-O possessed a dose- and time-dependent inhibitory effect against the proliferation of HepG2 cells. The IC50 value of Rh2-O for inhibition of HepG2 cell proliferation was 20.15 μM, which was roughly half the value of Rh2. Rh2-O induced apoptosis of HepG2 cells through a mitochondrial-mediated intrinsic pathway. In addition, the accumulation of ROS was detected in Rh2-O-treated HepG2 cells, which participated in the apoptosis of HepG2 cells. Conclusively, the findings above all suggested that Rh2-O as well as Rh2 inducing HepG2 cells apoptosis might involve similar mechanisms; however, Rh2-O had better antitumor activities than Rh2, probably due to its higher cellular uptake. PMID:26672619
In Vivo Early Intervention and the Therapeutic Effects of 20(S)-Ginsenoside Rg3 on Hypertrophic Scar Formation
Cheng, Liying; Sun, Xiaoming; Hu, Changmin; Jin, Rong; Sun, Baoshan; Shi, Yaoming
Background Intra-lesional injections of corticosteroids, interferon, and chemotherapeutic drugs are currently the most popular treatments of hypertrophic scar formation. However, these drugs can only be used after HS is formed, and not during the inflammatory phase of wound healing, which regulates the HS forming process. Objective To investigate a new, effective, combining therapeutic and safe drug for early intervention and treatment for hypertrophic scars. Methods Cell viability assay and flow cytometric analysis were studied in vitro. Animal studies were done to investigate the combining therapeutic effects of 20(S)-ginsenoside Rg3 (Rg3) on the inflammatory phase of wound healing and HS formation. Results In vitro studies showed that Rg3 can inhibit HS fibroblasts proliferation and induce HSF apoptosis in a concentration-dependent manner. In vivo studies demonstrated that Rg3 can limit the exaggerated inflammation, and do not delay the wound healing process, which indicates that Rg3 could be used as an early intervention to reduce HS formation. Topical injection of 4 mg/mL Rg3 can reduce HS formation by 34%. Histological and molecular studies revealed that Rg3 injection inhibits fibroblasts proliferation thus reduced the accumulation of collagen fibers, and down-regulates VEGF expression in the HS tissue. Conclusion Rg3 can be employed as an early intervention and a combining therapeutic drug to reduce inflammation and HS formation as well. PMID:25502572
Nanocomplexes based on amphiphilic hyaluronic acid derivative and polyethylene glycol-lipid for ginsenoside rg3 delivery.
Lee, Jae-Young; Yang, Heejung; Yoon, In-Soo; Kim, Sang-Bum; Ko, Seung-Hak; Shim, Jae-Seong; Sung, Sang Hyun; Cho, Hyun-Jong; Kim, Dae-Duk
Hybrid nanocomplex formulations, based on amphiphilic hyaluronic acid-ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents. PMID:25112537
Ginsenoside Rh1 Improves the Effect of Dexamethasone on Autoantibodies Production and Lymphoproliferation in MRL/lpr Mice
Feng, Yinglu; Wang, Chunbin; Cheng, Silu; Wang, Xiaorong; Meng, Xianze; Li, Lujia; Du, Juan; Liu, Qun; Guo, Yuyu; Meng, Yongbin; Cheng, Binbin; Ling, Changquan
Ginsenoside Rh1 is able to upregulate glucocorticoid receptor (GR) level, suggesting Rh1 may improve glucocorticoid efficacy in hormone-dependent diseases. Therefore, we investigated whether Rh1 could enhance the effect of dexamethasone (Dex) in the treatment of MRL/lpr mice. MRL/lpr mice were treated with vehicle, Dex, Rh1, or Dex + Rh1 for 4 weeks. Dex significantly reduced the proteinuria and anti-dsDNA and anti-ANA autoantibodies. The levels of proteinuria and anti-dsDNA and anti-ANA autoantibodies were further decreased in Dex + Rh1 group. Dex, Rh1, or Dex + Rh1 did not alter the proportion of CD4+ splenic lymphocytes, whereas the proportion of CD8+ splenic lymphocytes was significantly increased in Dex and Dex + Rh1 groups. Dex + Rh1 significantly decreased the ratio of CD4+/CD8+ splenic lymphocytes compared with control. Con A-induced CD4+ splenic lymphocytes proliferation was increased in Dex-treated mice and was inhibited in Dex + Rh1-treated mice. Th1 cytokine IFN-γ mRNA was suppressed and Th2 cytokine IL-4 mRNA was increased by Dex. The effect of Dex on IFN-γ and IL-4 mRNA was enhanced by Rh1. In conclusion, our data suggest that Rh1 may enhance the effect of Dex in the treatment of MRL/lpr mice through regulating CD4+ T cells activation and Th1/Th2 balance. PMID:25918545
Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4
Li, Xiaodong; Shan, Xiu; Wang, Xiaoqi; Yan, Qiu; Liu, Jiwei
The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. PMID:26636541
Core Bioactive Components Promoting Blood Circulation in the Traditional Chinese Medicine Compound Xueshuantong Capsule (CXC) Based on the Relevance Analysis between Chemical HPLC Fingerprint and In Vivo Biological Effects
Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei
Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and
Methyl jasmonate and salicylic acid elicitation induces ginsenosides accumulation, enzymatic and non-enzymatic antioxidant in suspension culture Panax ginseng roots in bioreactors.
Ali, Mohammad Babar; Yu, Kee-Won; Hahn, Eun-Joo; Paek, Kee-Yoeup
The effects of methyl jasmonate (MJ) and salicylic acid (SA) on changes of the activities of major antioxidant enzymes, superoxide anion accumulation (O2-), ascorbate, total glutathione (TG), malondialdehyde (MDA) content and ginsenoside accumulation were investigated in ginseng roots (Panax ginseng L.) in 4 l (working volume) air lift bioreactors. Single treatment of 200 microM MJ and SA to P. ginseng roots enhanced ginsenoside accumulation compared to the control and harvested 3, 5, 7 and 9 days after treatment. MJ and SA treatment induced an oxidative stress in P. ginseng roots, as shown by an increase in lipid peroxidation due to rise in O2- accumulation. Activity of superoxide dismutase (SOD) was inhibited in MJ-treated roots, while the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), SOD, guaiacol peroxidase (G-POD), glutathione peroxidase (GPx) and glutathione reductase (GR) were induced in SA-treated roots. A strong decrease in the activity of catalase (CAT) was obtained in both MJ- and SA-treated roots. Activities of ascorbate peroxidase (APX) and glutathione S transferase (GST) were higher in MJ than SA while the contents of reduced ascorbate (ASC), redox state (ASC/(ASC+DHA)) and TG were higher in SA- than MJ-treated roots while oxidized ascorbate (DHA) decreased in both cases. The result of these analyses suggests that roots are better protected against the O2- stress, thus mitigating MJ and SA stress. The information obtained in this work is useful for efficient large-scale production of ginsenoside by plant-root cultures. PMID:16463159
Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt
Park, E-K; Lee, EJ; Lee, S-H; Koo, KH; Sung, JY; Hwang, EH; Park, JH; Kim, C-W; Jeong, K-C; Park, B-K; Kim, Y-N
Background and purpose: Lipid rafts and caveolae are membrane microdomains with important roles in cell survival signalling involving the Akt pathway. Cholesterol is important for the structure and function of these microdomains. The ginsenoside Rh2 exhibits anti-tumour activity. Because Rh2 is structurally similar to cholesterol, we investigated the possibility that Rh2 exerted its anti-tumour effect by modulating rafts and caveolae. Experimental approach: A431 cells (human epidermoid carcinoma cell line) were treated with Rh2 and the effects on cell apoptosis, raft localization and Akt activation measured. We also examined the effects of over-expression of Akt and active-Akt on Rh2-induced cell death. Key results: Rh2 induced apoptosis concentration- and time-dependently. Rh2 reduced the levels of rafts and caveolae in the plasma membrane and increased their internalization. Furthermore, Akt activity was decreased and consequently, Akt-dependent phosphorylation of Bad, a pro-survival protein, was decreased whereas the pro-apoptotic proteins, Bim and Bax, were increased upon Rh2 treatment. Unlike microdomain internalization induce by cholesterol depletion, Rh2-mediated internalization of rafts and caveolae was not reversed by cholesterol addition. Also, cholesterol addition did not restore Akt activation or rescue cells from Rh2-induced cell death. Rh2-induced cell death was attenuated in MDA-MB-231 cells over-expressing either wild-type or dominant-active Akt. Conclusions and implications: Rh2 induced internalization of rafts and caveolae, leading to Akt inactivation, and ultimately apoptosis. Because elevated levels of membrane rafts and caveolae, and Akt activation have been correlated with cancer development, internalization of these microdomains by Rh2 could potentially be used as an anti-cancer therapy. PMID:20590613
Determination of ginsenoside compound K in human plasma by liquid chromatography–tandem mass spectrometry of lithium adducts
Chen, Yunhui; Lu, Youming; Yang, Yong; Chen, Xiaoyan; Zhu, Liang; Zhong, Dafang
Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography–tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile–water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00–1000 ng/mL (r2>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of −4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers. PMID:26579476
Ginsenoside-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis in rats
Ginsenoside-Rb3 (G-Rb3) has been previously demonstrated to attenuate myocardial ischemia-reperfusion injury (MIRI). The aim of the present study was to investigate this further and determine whether G-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis. Adult male Sprague Dawley rats were randomly divided into four groups: Sham, MIRI, G-Rb3 treatment (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The drug or placebo treatment was administered to the rats once a day for three consecutive days, and MIRI was then induced by subjecting the rats to left anterior descending coronary artery ligation for 30 min and reperfusion for 2 h. The results showed that G-Rb3 treatment significantly reduced the number of apoptotic cells in the myocardium and the expression of B-cell lymphoma 2-associated X protein, and increased the expression of B-cell lymphoma 2. The activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-MB in the serum were also reduced significantly by the G-Rb3 treatment. These findings suggest that G-Rb3 inhibits apoptosis in the early stage of MIRI, and attenuates MIRI when the reperfusion continues. G-Rb3 was also shown to significantly reduce the level of malondialdehyde and increase the activity of superoxide dismutase in the myocardium, which suggests that attenuating reactive oxygen species accumulation and oxidative stress may be the major mechanism underlying the anti-apoptotic effects of G-Rb3. The release of inflammatory factors was significantly attenuated by G-Rb3, which may also be associated with its anti-apoptotic effects. PMID:25371727
Metabolism of 20(S)-Ginsenoside Rg₂ by Rat Liver Microsomes: Bioactivation to SIRT1-Activating Metabolites.
Ma, Li-Yuan; Zhou, Qi-Le; Yang, Xin-Bao; Wang, Hong-Ping; Yang, Xiu-Wei
20(S)-Ginsenoside Rg₂ (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies on systematic metabolic profiles, the prospects for new drug development of 1 are still difficult to predict, which has become a huge obstacle for its safe clinical use. To solve this problem, investigation of the metabolic profiles of 1 in rat liver microsomes was first carried out. To identify metabolites, a strategy of combined analyses based on prepared metabolites by column chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. As a result, four metabolites M1-M4, including a rare new compound named ginsenotransmetin A (M1), were isolated and the structures were confirmed by spectroscopic analyses. A series of metabolites of 1, MA-MG, were also tentatively identified by UPLC-Q-TOF/MS in rat liver microsomal incubate of 1. Partial metabolic pathways were proposed. Among them, 1 and its metabolites M1, M3 and M4 were discovered for the first time to be activators of SIRT1. The SIRT1 activating effects of the metabolite M1 was comparable to those of 1, while the most interesting SIRT1 activatory effects of M3 and M4 were higher than that of 1 and comparable with that of resveratrol, a positive SIRT1 activator. These results indicate that microsome-dependent metabolism may represent a bioactivation pathway for 1. This study is the first to report the metabolic profiles of 1 in vitro, and the results provide an experimental foundation to better understand the in vivo metabolic fate of 1. PMID:27294899
Protective properties of ginsenoside Rb3 against UV-B radiation-induced oxidative stress in HaCaT keratinocytes.
Oh, Sun-Joo; Oh, Yuri; Ryu, In Wang; Kim, Kyunghoon; Lim, Chang-Jin
This work aimed to evaluate the skin anti-photoaging properties of ginsenoside Rb3 (Rb3), one of the main protopanaxdiol-type ginsenosides from ginseng, in HaCaT keratinocytes. The skin anti-photoaging activity was assessed by analyzing the levels of reactive oxygen species (ROS), pro-matrix metalloproteinase-2 (proMMP-2), pro-matrix metalloproteinase-9 (proMMP-9), total glutathione (GSH), and superoxide dismutase (SOD) activity as well as cell viability in HaCaT keratinocytes under UV-B irradiation. When HaCaT keratinocytes were exposed to Rb3 prior to UV-B irradiation, Rb3 exhibited suppressive activities on UV-B-induced ROS, proMMP-2, and proMMP-9 enhancements. On the contrary, Rb3 displayed enhancing activities on UV-B-reduced total GSH and SOD activity levels. Rb3 could not interfere with cell viabilities in UV-B-irradiated HaCaT keratinocytes. Rb3 plays a protective role against UV-B-induced oxidative stress in human HaCaT keratinocytes, proposing its potential skin anti-photoaging properties. PMID:26287932
Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.
Yu, Jing; Eto, Masato; Akishita, Masahiro; Kaneko, Akiyo; Ouchi, Yasuyoshi; Okabe, Tetsuro
Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells. PMID:17196933
Simultaneous determination of seven ginsenosides in rat plasma by high-performance liquid chromatography coupled to time-of-flight mass spectrometry: application to pharmacokinetics of Shenfu injection.
Li, Zhengguang; Zhang, Rui; Wang, Xiuping; Hu, Xiaofei; Chen, Yuguo; Liu, Qingfei
A high-performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-TOF MS) method was successfully developed and validated for the identification and determination of seven ginsenosides, Re , Rf , Rb1 , Rc , Rb2 , Ro and Rd , in a Chinese herbal preparation, Shenfu injection, and rat plasma. Based on the method, the pharmacokinetic profiles of the seven ginsenosides were investigated following intravenous administration of single dose of Shenfu injection to six rats. The established method had high linearity, selectivity, sensitivity, accuracy and precision. The pharmacokinetic results showed that Rb1 , Rc and Rb2 had similar pharmacokinetic profiles and relatively long half-life values (19.29 ± 6.36, 29.54 ± 22.91 and 35.60 ± 30.66 h). The half-lives of Rf and Rd were 4.21 ± 3.68 and 8.49 ± 5.20 h, respectively, indicating that they could be metabolized more rapidly than Rb1 , Rc and Rb2 . PMID:24935437
20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway.
Chen, Yi; Liu, Ze-Hong; Xia, Jing; Li, Xiao-Peng; Li, Ke-Qiong; Xiong, Wei; Li, Jing; Chen, Di-Long
Previous research has shown that total saponins of Panax ginseng (TSPG) and other ginsenoside monomers inhibit the proliferation of leukemia cells. However, the effect has not been compared among them. Cell viability was determined by Cell Counting Kit-8 assay, and ultra-structural characteristics were observed under transmission electron microscopy. Cell cycle distribution and apoptosis were determined by flow cytometry (FCM). Real-time fluorescence quantitative‑PCR, western blotting and immunofluorescence were used to measure the expression of β-catenin, TCF4, cyclin D1 and NF-κBp65. β-catenin/TCF4 target gene transcription were observed by ChIP-PCR assay. We found that 20(S)-ginsenoside Rh2 [(S)Rh2] inhibited the proliferation of KG-1a cells more efficiently than the other monomers. Moreover, (S)Rh2 arrested KG-1a cells in the G0/G1 phase and induced apoptosis. In addition, the levels of β-catenin, TCF4, cyclin D1 mRNA and protein were decreased. The ChIP-PCR showed that (S)Rh2 downregulated the transcription of β-catenin/TCF4 target genes, such as cyclin D1 and c-myc. These results indicated that (S)Rh2 induced cell cycle arrest and apoptosis through the Wnt/β-catenin signaling pathway, demonstrating its potential as a chemotherapeutic agent for leukemia therapy. PMID:27121661
Ginsenoside Rd Attenuates DNA Damage by Increasing Expression of DNA Glycosylase Endonuclease VIII-like Proteins after Focal Cerebral Ischemia
Yang, Long-Xiu; Zhang, Xiao; Zhao, Gang
Background: Ginsenoside Rd (GSRd), one of the main active ingredients in traditional Chinese herbal Panax ginseng, has been found to have therapeutic effects on ischemic stroke. However, the molecular mechanisms of GSRd's neuroprotective function remain unclear. Ischemic stroke-induced oxidative stress results in DNA damage, which triggers cell death and contributes to poor prognosis. Oxidative DNA damage is primarily processed by the base excision repair (BER) pathway. Three of the five major DNA glycosylases that initiate the BER pathway in the event of DNA damage from oxidation are the endonuclease VIII-like (NEIL) proteins. This study aimed to investigate the effect of GSRd on the expression of DNA glycosylases NEILs in a rat model of focal cerebral ischemia. Methods: NEIL expression patterns were evaluated by quantitative real-time polymerase chain reaction in both normal and middle cerebral artery occlusion (MCAO) rat models. Survival rate and Zea-Longa neurological scores were used to assess the effect of GSRd administration on MCAO rats. Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damages were evaluated by the way of real-time analysis of mutation frequency. NEIL expressions were measured in both messenger RNA (mRNA) and protein levels by quantitative polymerase chain reaction and Western blotting analysis. Apoptosis level was quantitated by the expression of cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay. Results: We found that GSRd administration reduced mtDNA and nDNA damages, which contributed to an improvement in survival rate and neurological function; significantly up-regulated NEIL1 and NEIL3 expressions in both mRNA and protein levels of MCAO rats; and reduced cell apoptosis and the expression of cleaved caspase-3 in rats at 7 days after MCAO. Conclusions: Our results indicated that the neuroprotective function of GSRd for acute ischemic stroke might be partially explained by the up
Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated kinase-mediated inhibition of microphthalmia-associated transcription factor
Lee, Seung Jae; Lee, Woo Jin; Chang, Sung Eun; Lee, Ga-Young
Background Panax ginseng has been used to prolong longevity and is believed to be useful for improving skin complexion. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has been demonstrated to possess antioxidative, antitumorigenic, and anti-inflammatory properties. The aim of this study was to examine the ability of G-Rg3 to inhibit melanogenesis. Methods The effects of G-Rg3 on melanin contents and the protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated. Melanogenesis-regulating signaling molecules such as Akt and extracellular signal-regulated kinase (ERK) were also examined to explore G-Rg3-induced antimelanogenic mechanisms. Results G-Rg3 was found to significantly inhibit the synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a dose-dependent manner. The activity of cellular tyrosinase and the expression of MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated. PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of melanin synthesis and tyrosinase activity. Conclusion Taken together, these results showed that G-Rg3 induces the activation of ERK, which accounts for its antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent, adding to the long list of uses of P. ginseng for the enhancement of skin beauty. PMID:26199555
Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng
Lin, Xiu-Xian; Peng, Shi-Fang; Xiao, Mei-Fang; Huang, Wei-Hua; Wang, Yi-Cheng; Peng, Jing-Bo; Zhang, Wei; Ouyang, Dong-Sheng; Chen, Yao
Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The Km and Vmax values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC50 values were 16.00 μM and 9.83 μM, and Ki values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors. PMID:26845774
Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.
Wu, Yizhen; Yu, Yinghua; Szabo, Alexander; Han, Mei; Huang, Xu-Feng
A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB pathway molecules (p-IKK and p-IκBα) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1β and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity. PMID:24675731
Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis.
Chen, Jingyu; Wu, Huaxun; Wang, Qingtong; Chang, Yan; Liu, Kangkang; Wei, Wei
Ginsenoside metabolite compound K (CK; 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, belongs to the dammarane-type triterpene saponins, according to its structure. The anti-inflammatory activity of CK has been identified in several studies. Our study demonstrated that CK exerted an anti-inflammatory effect in collagen-induced arthritis (CIA) and adjuvant-induced arthritis animal models, and this effect was due to inhibition of the abnormal activation and differentiation of T cells. However, the mechanism of CK in suppressing T-cell activation remains unclear. In this study, CK had a therapeutic effect in mice with CIA, decreased the percentage of activated T cells and dendritic cells (DCs), and increased the percentage of naive T cells in lymph nodes. The inhibitory effect on T-cell activation of CK was related to suppression of accumulation of DCs in lymph nodes. CK decreased CCL21 levels in lymph nodes and CCR7 expression in DCs and suppressed CCL21/CCR7-mediated migration of DCs, thus reducing accumulation of DCs in lymph nodes. In addition, signals for T-cell activation including major histocompatibility complex class II and costimulatory molecules, such as CD80 and CD86, were suppressed by CK, and the proliferation of T cells induced by DCs was inhibited by CK. In conclusion, this study demonstrated that CK downregulated DC priming of T-cell activation in CIA, and suppression of CCL21/CCR7-mediated DC migration and signaling between T cells and DCs might be the potential mechanism. These results provide an interesting, novel insight into the potential mechanism by which CK contributes to the anti-inflammatory effect in autoimmune conditions. PMID:25630466
Coupling of ultrasound-assisted extraction and expanded bed adsorption for simplified medicinal plant processing and its theoretical model: extraction and enrichment of ginsenosides from Radix Ginseng as a case study.
Mi, Jianing; Zhang, Min; Zhang, Hongyang; Wang, Yuerong; Wu, Shikun; Hu, Ping
A high-efficient and environmental-friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound-assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two-step elution protocol. The comparison results between the coupling of ultrasound-assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound-assisted extraction with expanded bed adsorption method rapidly increased by 1.4-fold and 18.5-fold of the conventional method, while the environmental cost and CO(2) emission of the conventional method were 12.9-fold and 17.0-fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound-assisted extraction with expanded bed adsorption system. PMID:23341270
NASA Astrophysics Data System (ADS)
Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si
There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.
Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors
Chen, Ronald JY; Jinn, Tzyy-rong; Chen, Yi-ching; Chung, Tse-yu; Yang, Wei-hung; Tzen, Jason TC
The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na+/K+-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na+/K+-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na+/K+-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na+/K+-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na+/K+-ATPase in the brain could be potential drugs for the treatment of ischemic stroke. PMID:21293466
Pseudoginsenoside F11, a Novel Partial PPARγ Agonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes
Wu, Guoyu; Yi, Junyang; Liu, Ling; Wang, Pengcheng; Zhang, Zhijie
PPARγ is a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPARγ agonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated from Panax quinquefolium L. (American ginseng). In this study, we found that p-F11 activates PPARγ with modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPARγ at Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPARγ agonist, which might have the potential to be developed as a new PPARγ-targeted therapeutics for type 2 diabetes. PMID:24454336
ERIC Educational Resources Information Center
Mechanic, David
Argues that culture change or modification of the social structure is necessary for effective health promotion because health behavior is closely tied to basic group structures and processes. Examines the health attitudes of Mormons, low income and minority groups, and developing Islamic nations, emphasizing attitudes towards education and women.…
Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma.
Zhou, Bo; Yan, Zhiping; Liu, Rong; Shi, Peng; Qian, Sheng; Qu, Xudong; Zhu, Liang; Zhang, Wei; Wang, Jianhua
Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may
Prevention of postoperative fatigue syndrome in rat model by ginsenoside Rb1 via down-regulation of inflammation along the NMDA receptor pathway in the hippocampus.
Chen, Wei-Zhe; Liu, Shu; Chen, Fan-Feng; Zhou, Chong-Jun; Yu, Jian; Zhuang, Cheng-Le; Shen, Xian; Chen, Bi-Cheng; Yu, Zhen
Postoperative fatigue syndrome (POFS) is a common complication which decelerates recovery after surgery. The present study investigated the anti-fatigue effect of ginsenoside Rb1 (GRb1) through the inflammatory cytokine-mediated N-methyl-D-aspartate (NMDA) receptor pathway. A POFS rat model was created by major small intestinal resection and assessed with an open field test. Real-time quantitative polymerase chain reaction, western blot analysis, high performance liquid chromatography and a transmission electron microscopic analysis were used to determine typical biochemical parameters in the hippocampus. Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. Degenerated neurons were found in the hippocampus of POFS rats. The NMDA receptor antagonist MK801 had a significant effect on central fatigue on postoperative day 1. GRb1 had no effect on IDO or tryptophan metabolism, but exhibited a significant effect on POFS by inhibiting the expression of inflammatory cytokines and NMDA receptor 1. These data suggested that inflammatory cytokines could activate tryptophan metabolism to cause POFS through the NMDA receptor pathway. GRb1 had an anti-fatigue effect on POFS by reducing inflammatory cytokines and NMDA receptors. PMID:25747983
The ginsenoside 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation.
Kang, Soouk; Kim, Jong-Eun; Song, Nu Ry; Jung, Sung Keun; Lee, Mee Hyun; Park, Jun Seong; Yeom, Myeong-Hun; Bode, Ann M; Dong, Zigang; Lee, Ki Won
Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma. PMID:25137374
Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice.
Shon, Jong Cheol; Shin, Hwa-Soo; Seo, Yong Ki; Yoon, Young-Ran; Shin, Heungsop; Liu, Kwang-Hyeon
The serum lipid metabolites of lean and obese mice fed normal or high-fat diets were analyzed via direct infusion nanoelectrospray-ion trap mass spectrometry followed by multivariate analysis. In addition, lipidomic biomarkers responsible for the pharmacological effects of compound K-reinforced ginsenosides (CK), thus the CK fraction, were evaluated in mice fed high-fat diets. The obese and lean groups were clearly discriminated upon principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) score plot, and the major metabolites contributing to such discrimination were triglycerides (TGs), cholesteryl esters (CEs), phosphatidylcholines (PCs), and lysophosphatidylcholines (LPCs). TGs with high total carbon number (>50) and low total carbon number (<50) were negatively and positively associated with high-fat diet induced obesity in mice, respectively. When the CK fraction was fed to obese mice that consumed a high-fat diet, the levels of certain lipids including LPCs and CEs became similar to those of mice fed a normal diet. Such metabolic markers can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, changes in the levels of such metabolites can be employed to assess the risk of obesity and the therapeutic effects of obesity management. PMID:25744175
Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling
Jung, Ji-Sun; Lee, Sang-Yoon; Kim, Dong-Hyun; Kim, Hee-Sun
Oxidative stress activates several intracellular signaling cascades that may have deleterious effects on neuronal cell survival. Thus, controlling oxidative stress has been suggested as an important strategy for prevention and/or treatment of neurodegenerative diseases. In this study, we found that ginsenoside Rh1 inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. Rh1 increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1, superoxide dismutase-2, and catalase, that are under the control of Nrf2/ARE signaling pathways. Further mechanistic studies showed that Rh1 increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to the antioxidant response element (ARE), and increased the ARE-mediated transcription activities in rat primary astrocytes. Analysis of signaling pathways revealed that MAP kinases are important in HO-1 expression, and act by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by Rh1 may provide preventive therapeutic potential for various neurodegenerative diseases that are associated with oxidative stress. PMID:26759699
Red ginseng protects against gentamicin-induced balance dysfunction and hearing loss in rats through antiapoptotic functions of ginsenoside Rb1.
Tian, Chun Jie; Kim, Seung Won; Kim, Yeon Ju; Lim, Hye Jin; Park, Raekil; So, Hong-Seob; Choung, Yun-Hoon
The authors evaluated the protective effects of Korean red ginseng (KRG) against gentamicin (GM)-induced unilateral vestibular and hearing dysfunction and investigated its effective mechanism using in vitro cell cultures. Vestibular function was comprehensively evaluated by a scoring system that ranged from 0 (normal) to 3 (worst) points, using head tilt, tail hanging, and swimming tests. The GM group showed significantly more deteriorated vestibular function (0 point--5 rats, 1 point--1 rat, 2 points--3 rats, and 3 points--3 rats) than the KRG+GM group (0 point--9 rats and 1 point--1 rat) (p<0.01). The hearing thresholds were better in the KRG+GM group than in the GM group (p<0.05). Quantitative analysis of hair cell damage in the scanning electron microscopy was closely related with vestibular and hearing functional results. In vitro study showed that ginsenoside Rb1 (gRb1) attenuated reactive oxygen species production, suppressed JNK activation, up-regulated Bcl-xL and down-regulated Bax, cytochrome c, caspase 3, and cleaved poly (ADP-ribose) polymerase in GM-treated VOT-E36 cells. These findings suggest that KRG including gRb1 component protects against vestibular/hearing dysfunction by inhibiting apoptotic pathways when ototoxicity is induced by unilateral intratympanic injection with GM in rats. PMID:23933362
Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.
Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min
Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. PMID:24375856
Anti-apoptotic Activity of Ginsenoside Rb1 in Hydrogen Peroxide-treated Chondrocytes: Stabilization of Mitochondria and the Inhibition of Caspase-3.
Na, Ji-Young; Kim, Sokho; Song, Kibbeum; Lim, Kyu-Hee; Shin, Gee-Wook; Kim, Jong-Hoon; Kim, Bumseok; Kwon, Young-Bae; Kwon, Jungkee
Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide (H2O2), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside Rb1 (GRb1) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and anti-tumor activities. In this study, we evaluated the effects of G-Rb1 on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by H2O2. Cultured rat articular chondrocytes were exposed to H2O2 with or without G-Rb1 and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-Rb1 showed an inhibition of MPT, caspase-3 activity, and cell death. Additionally, the levels of the apoptotic protein Bax were significantly lower and the levels of the anti-apoptotic protein Bcl-xL were higher compared with H2O2 treatment alone. The results of this study demonstrate that G-Rb1 protects chondrocytes against H2O2-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-Rb1 is a potentially useful drug for the treatment of OA patients. PMID:23717124
Ginsenoside Rg3 ameliorates lipopolysaccharide-induced acute lung injury in mice through inactivating the nuclear factor-κB (NF-κB) signaling pathway.
Cheng, Zhiqiang; Li, Li
Ginsenoside Rg3 (GRg3), one of the major active saponins isolated from ginseng (the root of Panax ginseng C.A. Meyer, Araliaceae), has been reported with many health benefits. Currently, the protective effect of GRg3 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice was investigated. The results indicated that GRg3 treatment could greatly attenuate LPS-induced histopathological alterations in the lung in a concentration-dependent manner. LPS-induced increase of lung wet-to-dry weight ratio (W/D ratio) was also dose-dependently reduced by GRg3 treatment. LPS-induced increases of the total cells, neutrophils and macrophages in the bronchoalveolar lavage fluids (BALFs) were significantly inhibited by GRg3 treatment in a dose-dependent fashion. The levels of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 in BALFs increased after LPS-induced ALI, which was inhibited by GRg3. Western blot results showed that during ALI LPS activated NF-κB pathway in the lung tissues by upregulating NF-κB p65 phosphorylation and its downstream COX-2 expression; however, these effects of LPS were inhibited by GRg3 treatment. Taken together, these findings in present study suggested that GRg3 provided protective effects against LPS-induced ALI in animal model and might harbor the potential to be considered as drug for the treatment of ALI in clinic. PMID:26921732
Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.
Tan, Shanjun; Yu, Wenkui; Lin, Zhiliang; Chen, Qiyi; Shi, Jialiang; Dong, Yi; Duan, Kaipeng; Bai, Xiaowu; Xu, Lin; Li, Jieshou; Li, Ning
Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20 mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-α, IL-1β, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with significance at doses of 10 and 20 mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis. PMID:25177041
Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase
Chen, Ronald JY; Chung, Tse-yu; Li, Feng-yin; Yang, Wei-hung; Jinn, Tzyy-rong; Tzen, Jason TC
Aim: To examine if steroid-like compounds found in many Chinese medicinal products conventionally used for the promotion of blood circulation may act as active components via the same molecular mechanism triggered by cardiac glycosides, such as ouabain. Methods: The inhibitory potency of ouabain and the identified steroid-like compounds on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of these compounds to Na+/K+-ATPase. Results: All the examined steroid-like compounds displayed more or less inhibition on Na+/K+-ATPase, with bufalin (structurally almost equivalent to ouabain) exhibiting significantly higher inhibitory potency than the others. In the pentacyclic triterpenoids examined, ursolic acid and oleanolic acid were moderate inhibitors of Na+/K+-ATPase, and their inhibitory potency was comparable to that of ginsenoside Rh2. The relatively high inhibitory potency of ursolic acid or oleanolic acid was due to the formation of a hydrogen bond between its carboxyl group and the Ile322 residue in the deep cavity close to two K+ binding sites of Na+/K+-ATPase. Moreover, the drastic difference observed in the inhibitory potency of ouabain, bufalin, ginsenoside Rh2, and pentacyclic triterpenoids is ascribed mainly to the number of hydrogen bonds and partially to the strength of hydrophobic interaction between the compounds and residues around the deep cavity of Na+/K+-ATPase. Conclusion: Steroid-like compounds seem to contribute to therapeutic effects of many cardioactive Chinese medicinal products. Chinese herbs, such as Prunella vulgaris L, rich in ursolic acid, oleanolic acid and their glycoside derivatives may be adequate sources for cardiac therapy via effective inhibition on Na+/K+-ATPase. PMID:20523340
Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets
Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin
Intracellular Ca2+ ([Ca2+]i) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca2+]i, which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit [Ca2+]i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca2+]i, which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658
Inhibitory Effects of Cytosolic Ca(2+) Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets.
Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin
Intracellular Ca(2+) ([Ca(2+)] i ) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca(2+)-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca(2+)] i , which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser(1756)) to inhibit [Ca(2+)] i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser(1756)) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca(2+) influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca(2+)-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658
Development of a sensitive LC-ESI-MS assay for 20(R)-ginsenoside Rh2 and its pharmacokinetic application in dogs
NASA Astrophysics Data System (ADS)
Gu, Yi; Wang, Guangji; Sun, Jianguo; Xie, Haitang; Jia, Yuanwei
20(R)-ginsenoside Rh2 is being developed as a new antitumor drug. To contribute to its biopharmaceutical and pharmacokinetic study, a novel LC-ESI-MS method was described in this paper and was proved to be accurate, precise and rugged with a linearity range of 0.5-200 ng/ml (r2 = 0.9998) in dog plasma. The method procedure consisted of an economical and simple liquid-liquid extraction with satisfactory recovery (>70%), and a subsequent rapid analysis (within 9.5 min) which was performed on a Shimadzu LCMS2010A system (electrospray ionization, Q-array-octapole-quadrupole mass analyzer), with an ODS column (150 mm × 2.0 mm i.d., 5 [mu]m) plus a C18 guard column for separation and ammonium chloride (500 [mu]mol) as mobile phase additive. Chlorinated adducts of molecular ions [M + Cl]- of 20(R)-Rh2 at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in select ion monitoring (SIM) mode of negative ions. The method showed an excellent sensitivity that the limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 20(R)-Rh2 were 0.1 and 0.5 ng/ml, respectively. This method was applied to a pharmacokinetic study of 20(R)-Rh2 in six dogs and the evaluation of the influence of micronization on pharmacokinetics. The results indicated micronization could remarkably improve the absolute bioavailability of 20(R)-Rh2.
Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1.
Bahem, Ruba; Hoffmann, Anja; Azonpi, Arnaud; Caballero-George, Catherina; Vanderheyden, Patrick
Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin. PMID:25519917
Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation.
Chen, Lei; Meng, Yue; Sun, Qi; Zhang, Zhongyu; Guo, Xiaoqing; Sheng, Xiaotong; Tai, Guihua; Cheng, Hairong; Zhou, Yifa
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. However, acquired resistance of cancer cells to TRAIL is a roadblock. Agents that can either potentiate the effect of TRAIL or overcome resistance to TRAIL are urgently needed. This article reports that ginsenoside compound K (CK) potentiates TRAIL-induced apoptosis in HCT116 colon cancer cells and sensitizes TRAIL-resistant colon cancer HT-29 cells to TRAIL. On a cellular mechanistic level, CK downregulated cell survival proteins including Mcl-1, Bcl-2, surviving, X-linked inhibitor of apoptosis protein and Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein, upregulated cell pro-apoptotic proteins including Bax, tBid and cytochrome c, and induced the cell surface expression of TRAIL death receptor DR5. Reduction of DR5 levels by siRNAs significantly decreases CK- and TRAIL-mediated apoptosis. Importantly, our results indicate, for the first time, that DR5 upregulation is mediated by autophagy, as blockade of CK-induced autophagy by 3-MA, LY294002 or Atg7 siRNAs substantially decreases DR5 upregulation and reduces the synergistic effect. Furthermore, CK-stimulated autophagy is mediated by the reactive oxygen species-c-Jun NH2-terminal kinase pathway. Moreover, we found that p53 and the C/EBP homologous (CHOP) protein is also required for DR5 upregulation but not related with autophagy. Our findings contribute significantly to the understanding of the mechanism accounted for the synergistic anticancer activity of CK and TRAIL, and showed a novel mechanism related with DR5 upregulation. PMID:27512955
Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury via Akt/GSK-3β Signaling and Inhibition of the Mitochondria-Dependent Apoptotic Pathway
Wang, Xiaoliang; Lau, Waynebond; Wang, Yajing; Xing, Yuan; Zhang, Xing; Ma, Xinliang; Gao, Feng
Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and apoptosis were assessed by flow cytometry. Mitochondrial membrane potential (MMP) was determined by 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family proteins, and phosphorylated Akt and GSK-3β were determined by western blot. Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and ±dP/dt. GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 µM) inhibited SI/R-induced ROS generation (P<0.01), decreased cellular apoptosis, stabilized the mitochondrial membrane potential (MMP), and attenuated cytosolic translocation of mitochondrial cytochrome c. GSRd inhibited activation of caspase-9 and caspase-3, increased the phosphorylated Akt and GSK-3β, and increased the Bcl-2/Bax ratio. Together, these data demonstrate GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway. PMID:23976968
Ginsenoside Rd Attenuates Mitochondrial Permeability Transition and Cytochrome c Release in Isolated Spinal Cord Mitochondria: Involvement of Kinase-Mediated Pathways
Zhou, Jin-Song; Wang, Jiang-Feng; He, Bao-Rong; Cui, Yong-Sheng; Fang, Xiang-Yi; Ni, Jian-Long; Chen, Jie; Wang, Kun-Zheng
Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. However, the effects of Rd on spinal cord mitochondrial dysfunction and underlying mechanisms are still obscure. In this study, we sought to investigate the in vitro effects of Rd on mitochondrial integrity and redox balance in isolated spinal cord mitochondria. We verified that Ca2+ dissipated the membrane potential, provoked mitochondrial swelling and decreased NAD(P)H matrix content, which were all attenuated by Rd pretreatment in a dose-dependent manner. In contrast, Rd was not able to inhibit Ca2+ induced mitochondrial hydrogen peroxide generation. The results of Western blot showed that Rd significantly increased the expression of p-Akt and p-ERK, but had no effects on phosphorylation of PKC and p38. In addition, Rd treatment significantly attenuated Ca2+ induced cytochrome c release, which was partly reversed by antagonists of Akt and ERK, but not p-38 inhibitor. The effects of bisindolylmaleimide, a PKC inhibitor, on Rd-induced inhibition of cytochrome c release seem to be at the level of its own detrimental activity on mitochondrial function. Furthermore, we also found that pretreatment with Rd in vivo (10 and 50 mg/kg) protected spinal cord mitochondria against Ca2+ induced mitochondrial membrane potential dissipation and cytochrome c release. It is concluded that Rd regulate mitochondrial permeability transition pore formation and cytochrome c release through protein kinases dependent mechanism involving activation of intramitochondrial Akt and ERK pathways. PMID:24897022
Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase
Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook
We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.
Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD, a natural inhibitor of the MDM2 oncogene: Nanoparticle preparation, characterization, in vitro and in vivo anti-prostate cancer activity, and mechanisms of action
Sarkar, Sushanta; Nag, Subhasree; Walbi, Ismail A.; Wang, Shu; Zhao, Yuqing; Wang, Wei; Zhang, Ruiwen
The Mouse Double Minute 2 (MDM2) oncogene plays a critical role in cancer development and progression through p53-dependent and p53-independent mechanisms. Both natural and synthetic MDM2 inhibitors have been shown anticancer activity against several human cancers. We have recently identified a novel ginsenoside, 25-OCH3-PPD (GS25), one of the most active anticancer ginsenosides discovered thus far, and have demonstrated its MDM2 inhibition and anticancer activity in various human cancer models, including prostate cancer. However, the oral bioavailability of GS25 is limited, which hampers its further development as an oral anticancer agent. The present study was designed to develop a novel nanoparticle formulation for oral delivery of GS25. After GS25 was successfully encapsulated into PEG-PLGA nanoparticles (GS25NP) and its physicochemical properties were characterized, the efficiency of MDM2 targeting, anticancer efficacy, pharmacokinetics, and safety were evaluated in in vitro and in vivo models of human prostate cancer. Our results indicated that, compared with the unencapsulated GS25, GS25NP demonstrated better MDM2 inhibition, improved oral bioavailability and enhanced in vitro and in vivo activities. In conclusion, the validated nano-formulation for GS25 oral delivery improves its molecular targeting, oral bioavailability and anticancer efficacy, providing a basis for further development of GS25 as a novel agent for cancer therapy and prevention. PMID:26041888
Stereoselective determination of ginsenosides Rg3 and Rh2 epimers in rat plasma by LC-MS/MS: application to a pharmacokinetic study.
Bae, Soo Hyeon; Zheng, Yu Fen; Yoo, Young Hyo; Kim, Jeom Yong; Kim, Sun Ok; Jang, Min Jung; Seo, Jae Hong; Bae, Soo Kyung
We developed and validated an accurate and sensitive LC-MS/MS method for the simultaneous quantitation of ginsenoside Rg3 and Rh2 epimers (R-Rg3, S-Rg3, R-Rh2, and S-Rh2) in rat plasma. Analytes were extracted from 0.1 mL aliquots of rat plasma by liquid-liquid extraction, using 2 mL of ethyl acetate. In this assay, dioscin (500 ng/mL) was used as an internal standard. Chromatographic separation was conducted using an Acclaim RSLC C18 column (150 × 2.1 mm, 2.2 μm) at 40°C, with a gradient mobile phase consisting of 0.1% formic acid in distilled water and in acetonitrile, a flow rate of 0.35 mL/min, and a total run time of 20 min. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with negative electrospray ionization at m/z 783.4 → 161.1 for R-Rg3 and S-Rg3, m/z 621.3 → 161.1 for R-Rh2 and S-Rh2, and m/z 867.2 → 761.5 for the internal standard. For R-Rg3 and S-Rg3, the lower limit of quantification was 5 ng/mL, with a linear range up to 500 ng/mL; for R-Rh2 and S-Rh2, the lower limit of quantification was 150 ng/mL, with a linear range up to 6000 ng/mL. The coefficient of variation for assay precision was less than 10.5%, with an accuracy of 86.4-112%. No relevant cross-talk or matrix effect was observed. The method was successfully applied to a pharmacokinetic study after oral administration of 400 mg/kg and 2000 mg/kg of BST204, a fermented ginseng extract, to rats. We found that the S epimers exhibited significantly higher plasma concentrations and area under curve values for both Rg3 and Rh2. This is the first report on the separation and simultaneous quantification of R-Rg3, S-Rg3, R-Rh2, and S-Rh2 in rat plasma by LC-MS/MS. The method should be useful in the clinical use of ginseng or its derivatives. PMID:23559579
Chryseobacterium ginsenosidimutans sp. nov., a bacterium with ginsenoside-converting activity isolated from soil of a Rhus vernicifera-cultivated field.
Im, Wan-Taek; Yang, Jung-Eun; Kim, Se-Young; Yi, Tae-Hoo
A Gram-reaction-negative, strictly aerobic, non-motile, non-spore-forming, rod-shaped bacterial strain, designated THG 15(T), was isolated from soil of a field cultivated with Rhus vernicifera in Okcheon province, South Korea, and its taxonomic position was investigated by using a polyphasic approach. Strain THG 15(T) grew optimally at 25-30 °C and at pH 7 in the absence of NaCl on nutrient agar. Strain THG 15(T) displayed β-glucosidase (aesculinase) activity that was responsible for its ability to transform ginsenoside Rb(1) (one of the dominant active components of ginseng) into compound K via Rd and F(2). On the basis of 16S rRNA gene sequence similarities, strain THG 15(T) was shown to belong to the family Flavobacteriaceae and was most closely related to Chryseobacterium soldanellicola PSD1-4(T) (97.7 % sequence similarity), Chryseobacterium soli JS6-6(T) (97.5 %) and Chryseobacterium indoltheticum LMG 4025(T) (97.3 %). The G+C content of the genomic DNA was 35.7 mol%. The major menaquinone was MK-6 and the major fatty acids were iso-C(15 : 0) (50.3 %), iso-C(17 : 0) 3-OH (21.9 %), summed feature 4 (comprising C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH; 9.5 %) and iso-C(17 : 1)ω9c (9.3 %). DNA sequence analysis and chemotaxonomic data supported the affiliation of strain THG 15(T) to the genus Chryseobacterium. DNA-DNA relatedness values between strain THG 15(T) and its closest phylogenetic neighbours were <15 %. Strain THG 15(T) could be differentiated genotypically and phenotypically from recognized species of the genus Chryseobacterium. The isolate therefore represents a novel species, for which the name Chryseobacterium ginsenosidimutans sp. nov. is proposed. The type strain is THG 15(T) ( = KACC 14527(T) = JCM 16719(T)). PMID:20656821
In vitro studies on the oxidative metabolism of 20(s)-ginsenoside Rh2 in human, monkey, dog, rat, and mouse liver microsomes, and human liver s9.
Li, Liang; Chen, Xiaoyan; Zhou, Jialan; Zhong, Dafang
20(S)-Ginsenoside Rh2 (Rh2)-containing products are widely used in Asia, Europe, and North America. However, extremely limited metabolism information greatly impedes the complete understanding of its clinical safety and effectiveness. The present study aims to systematically investigate the oxidative metabolism of Rh2 using a complementary set of in vitro models. Twenty-five oxidative metabolites were found using liquid chromatography-electrospray ionization ion-trap mass spectrometry. Six metabolites and a metabolic intermediate were synthesized. The metabolites were structurally identified as 26-hydroxy Rh2 (M1-1), (20S,24S)-epoxydammarane-12,25-diol-3-β-d-glucopyranoside (M1-3), (20S,24R)-epoxydammarane-12,25-diol-3-β-d-glucopyranoside (M1-5), 26,27-dihydroxy Rh2 (M3-6), (20S,24S)-epoxydammarane-12,25,26-triol-3-β-d-glucopyranoside (M3-10), (20S,24R)-epoxydammarane-12,25,26-triol-3-β-d-glucopyranoside (M3-11), and 26-aldehyde Rh2 on the basis of detailed mass spectrometry and nuclear magnetic resonance data analysis. Double-bond epoxidation followed by rearrangement and vinyl-methyl group hydroxylation represent the initial metabolic pathways generating monooxygenated metabolites M1-1 to M1-5. Further sequential metabolites (M2-M5) from the dehydrogenation and/or oxygenation of M1 were also detected. CYP3A4 was the predominant enzyme involved in the oxidative metabolism of Rh2, whereas alcohol dehydrogenase and aldehyde dehydrogenase mainly catalyzed the metabolic conversion of alcohol to the corresponding carboxylic acid. No significant differences were observed in the phase I metabolite profiles of Rh2 among the five species tested. Reactive epoxide metabolite formation in both humans and animals was evident. However, GSH conjugate M6 was detected only in cynomolgus monkey liver microsomal incubations. In conclusion, Rh2 is a good substrate for CYP3A4 and could undergo extensive oxidative metabolism under the catalysis of CYP3A4. PMID:22829543
Purification and Characterization of α-l-Arabinopyranosidase and α-l-Arabinofuranosidase from Bifidobacterium breve K-110, a Human Intestinal Anaerobic Bacterium Metabolizing Ginsenoside Rb2 and Rc
Shin, Ho-Young; Park, Sun-Young; Hwan Sung, Jong; Kim, Dong-Hyun
Two arabinosidases, α-l-arabinopyranosidase (no EC number) and α-l-arabinofuranosidase (EC 220.127.116.11), were purified from ginsenoside-metabolizing Bifidobacterium breve K-110, which was isolated from human intestinal microflora. α-l-Arabinopyranosidase was purified to apparent homogeneity, using a combination of ammonium sulfate fractionation, DEAE-cellulose, butyl Toyopearl, hydroxyapatite Ultrogel, QAE-cellulose, and Sephacryl S-300 HR column chromatography, with a final specific activity of 8.81 μmol/min/mg. α-l-Arabinofuranosidase was purified to apparent homogeneity, using a combination of ammonium sulfate fractionation, DEAE-cellulose, butyl Toyopearl, hydroxyapatite Ultrogel, Q-Sepharose, and Sephacryl S-300 column chromatography, with a final specific activity of 6.46 μmol/min/mg. The molecular mass of α-l-arabinopyranosidase was found to be 310 kDa by gel filtration, consisting of four identical subunits (77 kDa each, measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]), and that of α-l-arabinofuranosidase was found to be 60 kDa by gel filtration and SDS-PAGE. α-l-Arabinopyranosidase and α-l-arabinofuranosidase showed optimal activity at pH 5.5 to 6.0 and 40°C and pH 4.5 and 45°C, respectively. Both purified enzymes were potently inhibited by Cu2+ and p-chlormercuryphenylsulfonic acid. α-l-Arabinopyranosidase acted to the greatest extent on p-nitrophenyl-α-l-arabinopyranoside, followed by ginsenoside Rb2. α-l-Arabinofuranosidase acted to the greatest extent on p-nitrophenyl-α-l-arabinofuranoside, followed by ginsenoside Rc. Neither enzyme acted on p-nitrophenyl-β-galactopyranoside or p-nitrophenyl-β-d-fucopyranoside. These findings suggest that the biochemical properties and substrate specificities of these purified enzymes are different from those of previously purified α-l-arabinosidases. This is the first reported purification of α-l-arabinopyranosidase from an anaerobic Bifidobacterium sp. PMID:14660356
Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions
Zhang, Zhiyu; Du, Guang-Jian; Wang, Chong-Zhi; Wen, Xiao-Dong; Calway, Tyler; Li, Zejuan; He, Tong-Chuan; Du, Wei; Bissonnette, Marc; Musch, Mark W.; Chang, Eugene B.; Yuan, Chun-Su
Compound K (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC). A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC. PMID:23434653
Preparative isolation and purification of ginsenosides Rf, Re, Rd and Rb1 from the roots of Panax ginseng with a salt/containing solvent system and flow step-gradient by high performance counter-current chromatography coupled with an evaporative light scattering detector.
Qi, Xiaocheng; Ignatova, Svetlana; Luo, Guoan; Liang, Qionglin; Jun, Frank Wu; Wang, Yiming; Sutherland, Ian
Ginseng is a popular herb worldwide and has had varied uses in traditional Asian medicine for thousands of years. There are several different species of the herb, but all share the same constituents. Ginsenosides, the most extensively studied chemical components of ginseng, are generally considered to be one of the most important active ingredients of the plant. In this study, we have developed fast and efficient methodology for isolation of four known ginsenosides Rf, Rd, Re and Rb1 from Ginseng by high performance counter-current chromatography (HPCCC) coupled with evaporative light scattering detection (ELSD). The crude sample for HPCCC was purified firstly from a ginseng extraction using macroporous resin. The enriched saponin fraction (480 mg) was separated by using methylene chloride-methanol-5 mM aqueous ammonium acetate-isopropanol (6:2:4:3, v/v,) as the two-phase solvent system and yielded 10.7 mg of Rf, 11.0 mg of Rd, 13.4 mg of Re and 13.9 mg of Rb1. The purity of these ginsenosides was 99.2%, 88.3%, 93.7% and 91.8%, respectively assessed by HPLC-DAD-ELSD, and their structures were characterized by electrospray ionization mass spectrometry (ESI-MS) and compared with standards. Ammonium acetate was used to shorten the separation time and eliminate emulsification together with a flow step-gradient. The salt can be removed by re-dissolving the sample using acetone. PMID:20171644
Developing a Promotional Video
ERIC Educational Resources Information Center
Epley, Hannah K.
There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…
Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.
Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping
The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals. PMID:26783261
Chemical dampening of Ly6Chi monocytes in the periphery produces anti-depressant effects in mice
Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping
The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6Chi monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6Chi monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6Chi monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6Chi monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6Chi monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals. PMID:26783261
Buss, Paulo Marchiori; de Carvalho, Antonio Ivo
The evolution of health promotion within the Brazilian health system is examined, including an assessment of the intersectoral and development policies that have influenced the process. Particular attention is paid to the legal characteristics of the Unified Health System. Human resources formation and research initiatives in health promotion are outlined, with a summary of the obstacles that need to be overcome in order to ensure the effective implementation of health promotion in the future. Up to the end of the 20th Century health promotion was not used as a term in the Brazilian public heath context. Health promoting activities were concentrated in the area of health education, although targeting the social determinants of health and the principle of intersectoral action were part of the rhetoric. The situation has changed during the last decade, with the publication of a national policy of health promotion, issued by the Ministry of Health and jointly implemented with the States and Municipals Health Secretaries. More recently there has been a re-emergence of the discourse on the social determinants of health and the formation of intersectoral public policies as the basis of a comprehensive health promotion. Health promotion infrastructure, particularly around human resources and financing, requires strengthening in order to ensure capacity and sustainability in health promotion practice. PMID:18372870
High expression Zymomonas promoters
Viitanen, Paul V.; Tao, Luan; Zhang, Yuying; Caimi, Perry G.; McCole, Laura : Zhang, Min; Chou, Yat-Chen; McCutchen, Carol M.; Franden, Mary Ann
Identified are mutants of the promoter of the Z. mobilis glyceraldehyde-3-phosphate dehydrogenase gene, which direct improved expression levels of operably linked heterologous nucleic acids. These are high expression promoters useful for expression of chimeric genes in Zymomonas, Zymobacter, and other related bacteria.
Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells
Hwang, Yong Pil; Jeong, Hye Gwang
Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent Gbeta1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gbeta1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems.
77 FR 47820 - Invention Promoters/Promotion Firms Complaints
Federal Register 2010, 2011, 2012, 2013, 2014
... United States Patent and Trademark Office Invention Promoters/Promotion Firms Complaints ACTION: Proposed... concerning invention promoters and responses from the invention promoters to these complaints. An individual may submit a complaint concerning an invention promoter to the USPTO, which will forward the...
Promoting People's Participation.
ERIC Educational Resources Information Center
Fraser, Colin
Discusses problems associated with communication in rural areas to promote participation in development programs. Suggests that success of such programs depends on continued government policy in favor of citizen participation in agricultural and rural development. (SK)
ERIC Educational Resources Information Center
Raeder, Aggi
Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)
Winker, Margaret A.; Ferris, Lorraine E.
The Editor-in-Chief of the International Journal of MCH and AIDS (IJMA) is a member of the World Association of Medical Editors (WAME). The Editorial Board of IJMA believes it is important that the statement on promoting global health and this accompanying editorial is brought to the attention of our readers. Medical journal editors have a social responsibility to promote global health by publishing, whenever possible, research that furthers health worldwide.
Ivo de Carvalho, Antonio; Westphal, Marcia Faria; Pereira Lima, Vera Lucia Góes
Brazil, a Latin American country of continental proportions and contrasts, demographic inequalities, and social inequities, concomitantly faces the challenge of preventing and controlling infectious diseases, injuries, and non-communicable diseases. The loss of strength of the biomedical paradigm, the change in epidemiological profile, and the sociopolitical and cultural challenges of recent decades have fostered the emergence of new formulations about public health thinking and practice. Among them, are the paradigms of Brazilian Collective Health and Health Promotion. The former provides philosophical support for Brazil's Unified Health System (SUS). The aim of this article is to discuss the development of public health within the country's history, and to analyze and compare the theoretical assumptions of Health Promotion and Collective Health. We conclude that health promotion, based on the principles and values disseminated by the international Charters and concerned with social actors and social determinants of the health-disease process, has significant potential to promote the improvement of living and health conditions of the population. This frame of reference guided the formulation of the National Policy of Health Promotion within the Unified Health System, which was institutionalized by a ministerial decree. The importance and application of evaluating the effectiveness of health promotion processes and methodologies in Brazil have been guided by various frames of reference, which we clarify in this article through describing historical processes. PMID:17596091
Protective Effects of Panax Notoginseng Saponins on Cardiovascular Diseases: A Comprehensive Overview of Experimental Studies
Yang, Xiaochen; Xiong, Xingjiang; Wang, Heran; Wang, Jie
Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases. PMID:25152758
Evaluation of embryotoxicity for major components of herbal extracts using the chick embryonic heart micromass and mouse D3 embryonic stem cell systems.
Mohammed, Omar J; Latif, Muhammad Liaque; Pratten, Margaret K
Herbal remedies are often used during the early stages of pregnancy, being considered 'harmless' and 'natural'. There are insufficient data regarding their potential embryotoxicity. The main components of selected herbs, including 6-gingerol from ginger, Ginkgolide A and Ginkgolide B from gingko biloba and Ginsenoside Rg1 from ginseng, have been investigated using chick embryonic heart micromass and Mouse D3 embryonic stem cells. The potential effects were evaluated via alteration in contractility, cell viability, and cell protein content. The myocytes in both systems were also demonstrated by immunocytochemistry using a specific cardiomyocyte marker (α-actinin). For 6-gingerol, Ginkgolide A, Ginkgolide B and Ginsenoside Rg1 in both methods, at moderate to high concentrations, there were alterations in the values for the endpoints. These data indicate that herbal remedies used in the first trimester of pregnancy might not be safe for fetal development. PMID:26708230
Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion injury via Akt/endothelial nitric oxide synthase signaling and the B‑cell lymphoma/B‑cell lymphoma‑associated X protein pathway.
Wang, Yiping; Hu, Zhaohui; Sun, Bing; Xu, Jiahong; Jiang, Jinfa; Luo, Ming
Previous studies have suggested that ginsenoside Rg3 (GSRg3) extract from the medicinal plant Panax ginseng, may increase nitric oxide production via increases in the phosphorylation and expression of endothelial nitric oxide synthase (eNOS). The present study used an in vitro neonatal rat cardiomyocyte (NRC) model of anoxia‑reoxygenation injury and an in vivo rat model of myocardial ischemia/reperfusion (MI/R) injury. Hemodynamic, histopathological and biochemical assessment of the myocardial injury was performed and the expression levels of lactate dehydrogenase (LDH), superoxide dismutase and creatine kinase (CK) were measured in serum from the animal model, which may reflect myocardial injury. NRC injury was determined using a Cell Counting kit‑8. The GSRg3 anti‑apoptotic effects were assessed using flow cytometry to investigate the number of early‑late apoptotic cells and western blot analysis was performed to analyze the protein expression levels of caspase‑3, caspase‑9, B‑cell lymphoma‑2 (Bcl‑2), phosphorylated (p‑)Akt and eNOS. The results suggested that pretreatment with GSRg3 (60 mg/kg) significantly improved rat cardiac function, as demonstrated by increased left ventricular systolic pressure, heart rate and first derivative of left ventricular pressure. GSRg3 also reduced the size of the myocardial infarct and LDH/CK levels in the blood following MI/R. In vitro investigations revealed that GSRg3 (10 mM) decreased NRC apoptosis through inhibiting the activation of caspase‑3 and caspase‑9, and increasing the expression levels of p‑Akt, eNOS and the ratio of Bcl‑2/Bcl‑2‑associated X protein (Bax). Overall, the present study revealed that GSRg3 mediated a cardioprotective effect against MI/R‑induced apoptosis via Akt/eNOS signaling and the Bcl‑2/Bax pathway. PMID:25672441
Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice.
Sun, Jianhua; Hu, Songhua; Song, Xiaoming
Protopanaxadiol saponins (Rg3, Rd, Rc, Rb1 and Rb2) and protopanaxatriol saponins (Rg1, Re and Rg2) isolated from the root of Panax ginseng C.A. Meyer were evaluated for their adjuvant effects on the immune responses to ovalbumin (OVA) in mice. BALB/c mice were subcutaneously injected twice at a 3-week interval with 10 microg of ovalbumin or 10 microg of OVA plus 50 microg of ginsenosides Rg3, Rd, Rc, Rb1, Rb2, Rg1, Re or Rg2 or Quil A (n=5). Blood samples were collected for measuring specific total-IgG, IgG1 and IgG2a, and splenocytes were harvested for determining lymphocyte proliferation as well as IFN-gamma and IL-5 production 2 weeks after the boosting. The results indicated that OVA-specific antibody responses were significantly higher in mice immunized with OVA co-administered with Rg1, Re, Rg2, Rg3 and Rb1 but not with Rd, Rc and Rb2 when compared with the control (immunized with OVA only). Significantly enhanced splenocyte proliferative responses to Con A, LPS and OVA as well as the production of both IL-5 and IFN-gamma stimulated by OVA were also detected in mice immunized with OVA co-administered with Rg1 but not with Rb1, Re and Rg3. Of the ginsenosides studied, Rg1, Re, Rg2, Rg3 and Rb1 have more potent adjuvant properties than the others, indicating that they are the major constituents contributing to the adjuvant activities of total ginseng saponins. Varieties of ginsenosides in adjuvant activity might be attributed to the varieties of molecular conformations determined by the side sugar chains attaching to their dammarane skeleton. PMID:17069940
Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.
Wang, Minchao; Lu, Yanzhen; Liu, Jiangang; Li, Hao; Wei, Yun
Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug. PMID:26138785
Act To Promote Adult Education.
ERIC Educational Resources Information Center
An act of the German Lower Saxony Parliament to promote adult education is presented. It has 24 general provisions relating to the following: purpose of adult education, principle for promotion, conditions for promotions of establishments, independence of adult education, prerequisites and form of acknowledgement of entitlement to promotion,…
Promoting Healthy Dietary Behaviors.
ERIC Educational Resources Information Center
Perry, Cheryl L.; Story, Mary; Lytle, Leslie A.
This chapter reviews the research on promoting healthy dietary behaviors in all youth, not just those who exhibit problems such as obesity or eating disorders. The first section of this chapter presents a rationale for addressing healthy dietary behavior with children and adolescents, on the basis of the impact of these behaviors on short- and…
Health Promotion Interventions.
ERIC Educational Resources Information Center
Jason, Leonard A.; Curie, Carrie J.; Townsend, Stephanie M.; Pokorny, Steven B.; Katz, Richard B.; Sherk, Joseph L.
Reviews four areas from the prevention science field, including: promoting healthy behavior; preventing substance abuse; preventing high-risk sexual behaviors; and preventing child abuse and sexual abuse. Recommendations are made regarding strategies for implementing empirically validated programs, supplementing school programs with ecological…
ERIC Educational Resources Information Center
Pluviose, David
Launched in 1985 at Arizona State University, the Hispanic Research Center's (HRC) efforts to promote Latino and Chicano art and issues have flourished in recent years. In 2004, the HRC hosted the Arizona International Latina/o Arts Festival in collaboration with the Mesa Southwest Museum. The HRC has also founded a mentoring institute for…
Partners: Promoting Accessible Recreation.
ERIC Educational Resources Information Center
Sable, Janet; Gravink, Jill
The Promoting Accessible Recreation through Networking, Education, Resources and Services (PARTNERS) Project, a partnership between Northeast Passage, the University of New Hampshire, and Granite State Independent Living Foundation, helps create barrier-free recreation for individuals with physical disabilities. The paper describes PARTNERS and…
ERIC Educational Resources Information Center
Madeyski, Tom
Includes 50 cost-effective ideas for promoting camp in the areas of recruiting new campers, encouraging returning campers, advertising strategies, printing brochures and other written materials, using photographs, targeting groups for camp facility rental, and effectively using the media. (LP)
Homeopathy: promotion versus evidence.
Ernst, E
Homeopathy is a biologically implausible form of treatment. The best clinical evidence available to date fails to support its effectiveness. Nevertheless, it is gaining in popularity. One reason for this is that, at least in the UK, it is being promoted by influential people. PMID:19442345
Pseudorevertants of a lac promoter mutation reveal overlapping nascent promoters.
Karls, R; Schulz, V; Jovanovich, S B; Flynn, S; Pak, A; Reznikoff, W S
Four pseudorevertants of a -10 region lacP mutation were isolated. Three of these mutations were found to activate nascent promoters. These mutations were: a -2 G/C----A/T change (-2A) promoting transcription at position +11, a +1 A/T----T/A change (+1T) promoting transcription initiation at position +13, and a +10 C/G----A/T change (+10A) promoting transcription initiation at a complex series of positions. The fourth mutation [a -12 T/A----A/T change (-12A)] promotes transcription initiation at -1. The promoters activated by mutations -12A, -2A and +1T resembled the canonical sigma 70 promoter sequences. The +10A promoter activity is also dependent upon the sigma 70 holoenzyme but can not be readily assigned to a specific promoter sequence. Images PMID:2499870
[Promoting Living Kidney Transplantation].
Lin, Chiu-Chu
Kidney transplantation is the best approach for treating patients with end stage renal disease, offering patients the best chance of returning to normal health. While the techniques used in kidney transplantation surgery are mature and highly successful, there is a severe shortage of donor organs. Statistics show a serious imbalance between organ donations and patients on the waiting list for organ transplantation. Moreover, evidence from empirical studies has shown a better transplantation outcome for patients who receive living donor transplantation than for those who receive organs from cadavers. Although using relatives as donors offers an effective way to reduce the problem of organ shortage, this strategy faces many challenges and many other factors affect the promotion of living donor transplantation. This article elaborates how cultural and psychological factors, kidney transplantation awareness, and ethics and laws impact upon living kidney donations and then proposes coping strategies for promoting living kidney transplantation. PMID:27026555
Human Promoters Are Intrinsically Directional
Duttke, Sascha H.C.; Lacadie, Scott A.; Ibrahim, Mahmoud M.; Glass, Christopher K.; Corcoran, David L.; Benner, Christopher; Heinz, Sven; Kadonaga, James T.; Ohler, Uwe
Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that up to half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. PMID:25639469
The promotion of breastfeeding.
Tuluhungwa, R R; Yung, W
To reverse the current trend of a significant decline worldwide in breast feeding means reeducation of medical and health personnel as well as the general public. Programs to promote breast feeding require the commitment of governments, with support from various ministries including health, education, labor, community development and judiciary. Examples of what 3 developing countries--Jamaica, Colombia and Thailand--are doing to promote breast feeding are reported. A large scale breast feeding campaign was launched in Jamaica in October 1977. The 3 phases of the campaign were: 1) preliminary surveys and research and motivation of professional, voluntary and extension groups through training seminars, panel discussions, and meetings; 2) promotion of breast feeding via mass media and motivation of target groups by trained personnel; and 3) evaluation of the campaign. A survey undertaken in 1978 showed that the breast feeding messages had achieved the desired effect--more mothers practiced breast feeding. In Colombia the breast feeding campaign emphasized non-formal education through the use of games and pictures. A game is used which is usually initiated by a health worker in the waiting room of a health center and involves the mothers, the general public, and sometimes the professional personnel. Through reading and interpreting rhymed breast feeding messages, the participants exchange opinions and experiences. Before starting a campaign to encourage low-income urban and semi-urban mothers to breast feed, the National Food and Nutrition Committee of Thailand pretested slogans and posters designed for the promotion of breast feeding. Posters develpoed in accordance with the suggestions made by the women were tested among 126 pregnant and lactating women. The Committee decided which picture to print for low-income and rural audiences and which to print for middle-class audiences. PMID:12336781
Promoter propagation in prokaryotes.
Matus-Garcia, Mariana; Nijveen, Harm; van Passel, Mark W J
Transcriptional activation or 'rewiring' of silent genes is an important, yet poorly understood, phenomenon in prokaryotic genomes. Anecdotal evidence coming from experimental evolution studies in bacterial systems has shown the promptness of adaptation upon appropriate selective pressure. In many cases, a partial or complete promoter is mobilized to silent genes from elsewhere in the genome. We term hereafter such recruited regulatory sequences as Putative Mobile Promoters (PMPs) and we hypothesize they have a large impact on rapid adaptation of novel or cryptic functions. Querying all publicly available prokaryotic genomes (1362) uncovered >4000 families of highly conserved PMPs (50 to 100 long with ≥80% nt identity) in 1043 genomes from 424 different genera. The genomes with the largest number of PMP families are Anabaena variabilis (28 families), Geobacter uraniireducens (27 families) and Cyanothece PCC7424 (25 families). Family size varied from 2 to 93 homologous promoters (in Desulfurivibrio alkaliphilus). Some PMPs are present in particular species, but some are conserved across distant genera. The identified PMPs represent a conservative dataset of very recent or conserved events of mobilization of non-coding DNA and thus they constitute evidence of an extensive reservoir of recyclable regulatory sequences for rapid transcriptional rewiring. PMID:22933716
Simone, G. A.
The objective of this Bicycle Promotion Plan is to outline a set of recommendations and supporting strategies for implementation by the US DOE toward increased use of the bicycle for energy conservation. The recommendations are designed in such a way as to function in concert with: (1) bicycle programs administered by other Federal government agencies; and (2) related programs and activities already sponsored by DOE. The approach to preparation of the Plan involved a review of all current and planned bicycle promotion programs at the Federal level as well as a review of the array of lierature on the subject. The UniWorld project staff also interacted with several DOE program offices, in order to determine the extent to which they might appropriately contribute to the implementation of bicycle promotional efforts. A synthesis of all the information gathered was published in January of 1981 as a part of the project (The Bicycle Program Review). Based upon this information and an examination of the barriers to bicycle use identified by bicycle transportation specialists in the field, UniWorld developed a series of the most potentially effective recommendations and program strategies for implementation by DOE. The recommendations address activities that could be undertaken in conjunction with existing DOE programs, new developments that might be considered to fulfill critical needs in the field, and interagency efforts that DOE could play a role in.
Promoter occlusion: transcription through a promoter may inhibit its activity.
Adhya, S; Gottesman, M
Induction of prophage lambda inhibits the expression of the gal operon from its cognate promoters. The effect is observed only in cis, and is due to frequent transcription of the gal promoter region by RNA polymerase molecules initiating upstream at the prophage PL promoter. The frequency of transcription initiation at PL is some 30 times greater than that at the gal promoter, Pg1. PL is one of the strongest procaryotic promoters. This "promoter occlusion" is essentially complete when the distance between gal and PL is small (less than or equal to 10 kb); and when PL is fully active (that is, in the absence of the cl or cro repressors). We discuss the possibility that promoter occlusion at two lambda promoters, Pint and PR', might play a role in the sequential expression of viral functions. PMID:6217898
The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats.
Martinez, B; Staba, E J
Relative and total amount of saponins in Panax ginseng, Panax quinquefolius, Aralia mandshurica and Eleutherococcus senticosus were determined by thin-layer chromatography and by a spectrophotometric method. The ginsenoside Rg1 was present in American ginseng. Aralia and Eleutherococcus did not contain diol- and triol-type ginsenosides. Low concentrations of ginsenosides were found in Oriental red ginsengs (1.4-2.7%). Orally administered Araliaceae saponin extracts did not affect plasma lactic acid, glucagon, insulin or liver glycogen levels in exercised rats and did not prolong their swimming time. Plasma glucose levels in resting rats were decreased by saponin extracts of Canadian white, American red, Sanchi, Aralia, Eleutherococcus, Korean red and Shiu-Chi ginsengs. PMID:6379247
PROMOTIONS: PROper MOTION Software
NASA Astrophysics Data System (ADS)
Caleb Wherry, John; Sahai, R.
We report on the development of a software tool (PROMOTIONS) to streamline the process of measuring proper motions of material in expanding nebulae. Our tool makes use of IDL's widget programming capabilities to design a unique GUI that is used to compare images of the objects from two epochs. The software allows us to first orient and register the images to a common frame of reference and pixel scale, using field stars in each of the images. We then cross-correlate specific morphological features in order to determine their proper motions, which consist of the proper motion of the nebula as a whole (PM-neb), and expansion motions of the features relative to the center. If the central star is not visible (quite common in bipolar nebulae with dense dusty waists), point-symmetric expansion is assumed and we use the average motion of high-quality symmetric pairs of features on opposite sides of the nebular center to compute PM-neb. This is then subtracted out to determine the individual movements of these and additional features relative to the nebular center. PROMOTIONS should find wide applicability in measuring proper motions in astrophysical objects such as the expanding outflows/jets commonly seen around young and dying stars. We present first results from using PROMOTIONS to successfully measure proper motions in several pre-planetary nebulae (transition objects between the red giant and planetary nebula phases), using images taken 7-10 years apart with the WFPC2 and ACS instruments on board HST. The authors are grateful to NASA's Undergradute Scholars Research Program (USRP) for supporting this research.
Doyal, L
The male-dominated medical establishment continues to make health promotion policies for women. Women must have access to a more accurate information base about women's health and the link between their health and socioeconomic roles. They must be full partners in formulating and implementing health promotion strategies. Yet, such a database does not exist due to systemic bias in research. For example, research shows alcoholism affects men and women differently, but prevention and treatment strategies and evaluation of their outcomes do not take this into account. Further, men do not understand subjective aspects of female conditions. In addition, even though women provide most care in our society, health promotion policies do not incorporate their knowledge. Moreover, care of the sick can damage the health of the care giver. Statistics on women's health are lacking, e.g., exhaustion and depression as consequences of child care and housework, especially among poor women. Developed countries continue to use maternal mortality as a means of measuring reproductive hazard, but maternal death is a rarity. In fact, a reproductive mortality rate would be more applicable, which would include deaths from abortions, pregnancy, and contraception. Besides, birth control has real disadvantages, e.g., a painful medical procedure is needed to insert IUDs and they increase the risk of pelvic inflammatory disease. Paid employment has positive and negative effects depending on whether women are alone or have a partner and have children, their income, and educational level. Women in industry face considerable health hazards, e.g., textile workers at increased risk of several lung diseases. Appropriate expenditure on health and social services and sound economic policies at the central level will benefit women's health. Besides, when society values and supports all aspects of women's work and roles, women's health will achieve its potential. PMID:1817541
Price, Bob
Nurses are accustomed to helping others with their sleep problems and dealing with issues such as pain that may delay or interrupt sleep. However, they may be less familiar with what constitutes a healthy night's sleep. This article examines what is known about the process and purpose of sleep, and examines the ways in which factors that promote wakefulness and sleep combine to help establish a normal circadian rhythm. Theories relating to the function of sleep are discussed and research is considered that suggests that sleep deficit may lead to metabolic risks, including heart disease, obesity, type 2 diabetes mellitus and several types of cancer. PMID:26959472
An initiation promotion bioassay for chemical carcinogens and tumor promoters has been developed in rat liver using presumed preneoplastic lesions, foci of gamma-glutamyltranspeptidase (GGTase)-positive hepatocytes, as the endpoint. To evaluate the tumor-promoting activity of phe...
Amelio, Ivano; Antonov, Alexey A.; Catani, Maria Valeria; Massoud, Renato; Bernassola, Francesca; Knight, Richard A.; Melino, Gerry; Rufini, Alessandro
Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation. PMID:25514460
Tryptophan promotes charitable donating
Steenbergen, Laura; Sellaro, Roberta; Colzato, Lorenza S.
The link between serotonin (5-HT) and one of the most important elements of prosocial behavior, charity, has remained largely uninvestigated. In the present study, we tested whether charitable donating can be promoted by administering the food supplement L-Tryptophan (TRP), the biochemical precursor of 5-HT. Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation. As expected, compared to a neutral placebo, TRP appears to increase the participants' willingness to donate money to a charity. This result supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others. PMID:25566132
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion..., including domestic and international markets, and to stimulate sales of peanuts....
Oxytocin promotes human ethnocentrism.
De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J
Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence. PMID:21220339
Environmental Health Promotion: Bridging Traditional Environmental Health and Health Promotion
ERIC Educational Resources Information Center
Howze, Elizabeth H.; Baldwin, Grant T.; Kegler, Michelle Crozier
This article highlights the juncture between environmental health and health promotion and underscores the need for health promotion involvement in environmental health practice. It begins with a synopsis of current issues in environmental public health and deficiencies in environmental public health practice that could be partly ameliorated by an…
Health-promoting schools: an opportunity for oral health promotion.
Kwan, Stella Y. L.; Petersen, Poul Erik; Pine, Cynthia M.; Borutta, Annerose
Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated framework and appropriate methodologies for the evaluation of school oral health projects is emphasized. PMID:16211159
Insurance Incentives for Health Promotion.
ERIC Educational Resources Information Center
Hosokawa, Michael C.
To reduce the cost of reimbursements, many insurance companies have begun to use insurance incentives as a way to motivate individuals to participate in health promotion activities. Traditional health education, research and demonstration, and policy-premium incentives are methods of health promotion used by life and health insurance companies.…
Health promotion: awarding good practice.
Davison, Heather; Griffiths, John
Dr Heather Davison, Director of Development at the Royal Society for Public Health (RSPH), and John Griffiths, Programme Manager for the Health-Promoting Workforce, provide an overview of the RSPH's Health-Promoting Organization Awards--highlighting the achievements of the 2009 winners while learning for the future. PMID:20642127
Promoting Creativity in Young Children.
ERIC Educational Resources Information Center
Honig, Alice Sterling
This paper discusses creativity in young children and what teachers can do to support and promote it. Topics addressed in the paper include: (1) teacher interest in promoting creativity; (2) defining creativity; (3) creativity in the socioemotional domain; (4) the relationship between creativity and empathy for others; (4) bibliotherapy; (5)…
Promoting Reading in Developing Countries.
ERIC Educational Resources Information Center
Greaney, Vincent, Ed.
With the intention of illuminating the many obstacles involved with literacy promotion in the developing nations of Africa, Asia, and South America, the authors of the 10 articles in this collection share their knowledge and experience of literacy promotion in the developing world--including the unique challenges faced by those who publish, print,…
Photovoltaic module with adhesion promoter
Xavier, Grace
Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.
Zoning should promote public health.
Hirschhorn, Joel S
Legally, governments use their police powers to protect public health, safety, and welfare through zoning. This paper presents a case for revisiting zoning on the basis of increasing evidence that certain types of community design promote public health, as opposed to the dominant pattern of sprawl development, which does not. Zoning, and the land use planning linked to it, that prohibits or disfavors health-promoting community designs contradicts the inherent public policy goal on which it is based. If there is a paradigm shift underway, from traditional sprawl to health-promoting community designs, then health professionals and others should understand why zoning must be reassessed. PMID:14748317
Nutritional Recommendation Should Promote Sustainability.
ERIC Educational Resources Information Center
Reber, Robert J.
Any process or event that disrupts the flow of nutrients and energy becomes a nutrition problem. Nutritionists should promote practices that protect the integrity, stability, and beauty of the land community (soil, water, air, all biological species). (Author)
Code of Federal Regulations, 2010 CFR
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1250.310 Section 1250.310 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.310 Promotion. Promotion means any action, including...
Code of Federal Regulations, 2010 CFR
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1210.312 Section 1210.312 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means...
Code of Federal Regulations, 2010 CFR
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1260.122 Section 1260.122 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions § 1260.122 Promotion. Promotion means any action, including...
Code of Federal Regulations, 2010 CFR
... and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.114 Promotion. Promotion means actions such as paid advertising, sales... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1150.114 Section 1150.114...
Code of Federal Regulations, 2010 CFR
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1206.17 Section 1206.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion...
Hine, Christopher M; Li, Hongjie; Xie, Li; Mao, Zhiyong; Seluanov, Andrei; Gorbunova, Vera
The DNA double-strand break repair and homologous recombination protein Rad51 is overexpressed in the majority of human cancers. This correlates with therapy resistance and decreased patient survival. We previously showed that constructs containing Rad51 promoter fused to a reporter gene are, on average, 850-fold more active in cancer cells than in normal cells. It is not well understood what factors and sequences regulate the Rad51 promoter and cause its high activity in cancerous cells. Here we characterized regulatory regions and examined genetic requirements for oncogenic stimulation of the Rad51 promoter. We identified specific regions responsible for up- and downregulation of the Rad51 promoter in cancerous cells. Furthermore, we show that Rad51 expression is positively regulated by EGR1 transcription factor. We then modeled the malignant transformation process by expressing a set of oncoproteins in normal human fibroblasts. Expression of different combinations of SV40 large T antigen, oncogenic Ras and SV40 small T antigen resulted in step-wise increase in Rad51 promoter activity, with all the 3 oncoproteins together leading to a 47-fold increase in expression. Cumulatively, these results suggest that Rad51 promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy. PMID:24781030
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research... promotion, and publicity to advance the image and sales of, and demand for, dairy products generally....
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research... promotion, and publicity to advance the image and sales of, and demand for, dairy products generally....
Creating and Promoting a Natural History Collection.
ERIC Educational Resources Information Center
Belben, Cathy
Discusses the value of developing and promoting a natural history library by school library media specialists. Topics include benefits to students; promoting outdoor education; recommended reading for high school students; using technology; and other aids to promote outdoor education. (LRW)
Health promotion: a global perspective.
Kickbusch, I
The first part of this paper reviews the work of the World Health Organization's Regional Office for Europe undertaken to clarify the relevance of health promotion for all member states and regions. This work led to a definition of "health" as the ability to realize aspirations and satisfy needs and to change or cope with the environment. Health promotion was considered to 1) involve the population as a whole in the context of everyday lives, 2) be directed towards action on the determinants of health, 3) combine diverse but complementary methods or approaches, 4) aim for effective and concrete public participation, and 5) involve health professionals. Areas covered by health promotion activities include 1) access to health, 2) development of an environment conductive to health, 3) strengthening of social networks and social supports, 4) promoting positive health behavior and appropriate coping strategies, and 5) increasing knowledge and disseminating information. The next section of the paper traces the development of the concept of health promotion from its roots in health education, and the third section presents a brief history of public health to contextualize this development. The differences between the old and new approaches to public health are presented (the new role of the health sector is to ensure access to health, create advocacy for health, and move beyond health care through intersectoral action and public participation), and the new "forcefield" of public health that emerges from a conceptualization of health promotion is described. This forcefield, illustrated as a triangle linking healthy public policy, health promotion, and community action, works at all levels and is the framework for the development of appropriate strategies. It is concluded that in many cases public health will have to be reorganized as will the health care system as a whole. Health must be viewed as a social project linked to political responsibilities not as a medical
Alteration of Panax ginseng saponin composition by overexpression and RNA interference of the protopanaxadiol 6-hydroxylase gene (CYP716A53v2)
Park, Seong-Bum; Chun, Ju-Hyeon; Ban, Yong-Wook; Han, Jung Yeon; Choi, Yong Eui
Background The roots of Panax ginseng contain noble tetracyclic triterpenoid saponins derived from dammarenediol-II. Dammarene-type ginsenosides are classified into the protopanaxadiol (PPD) and protopanaxatriol (PPT) groups based on their triterpene aglycone structures. Two cytochrome P450 (CYP) genes (CYP716A47 and CYP716A53v2) are critical for the production of PPD and PPT aglycones, respectively. CYP716A53v2 is a protopanaxadiol 6-hydroxylase that catalyzes PPT production from PPD in P. ginseng. Methods We constructed transgenic P. ginseng lines overexpressing or silencing (via RNA interference) the CYP716A53v2 gene and analyzed changes in their ginsenoside profiles. Result Overexpression of CYP716A53v2 led to increased accumulation of CYP716A53v2 mRNA in all transgenic roots compared to nontransgenic roots. Conversely, silencing of CYP716A53v2 mRNA in RNAi transgenic roots resulted in reduced CYP716A53v2 transcription. HPLC analysis revealed that transgenic roots overexpressing CYP716A53v2 contained higher levels of PPT-group ginsenosides (Rg1, Re, and Rf) but lower levels of PPD-group ginsenosides (Rb1, Rc, Rb2, and Rd). By contrast, RNAi transgenic roots contained lower levels of PPT-group compounds and higher levels of PPD-group compounds. Conclusion The production of PPD- and PPT-group ginsenosides can be altered by changing the expression of CYP716A53v2 in transgenic P. ginseng. The biological activities of PPD-group ginsenosides are known to differ from those of the PPT group. Thus, increasing or decreasing the levels of PPT-group ginsenosides in transgenic P. ginseng may yield new medicinal uses for transgenic P. ginseng. PMID:26843821
Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen.
He, Nian-Wu; Zhao, Yan; Guo, Ling; Shang, Jun; Yang, Xing-Bin
Dietary and medicinal uses of Panax notoginseng have been associated with reduced risk of cancer. This study was designed to investigate the profiles of P. notoginseng saponin extract (PNSE), the major bioactive ingredients in P. notoginseng (Burk.) F.H. Chen, by high-performance liquid chromatography, and, for the first time, the anticancer effect of PNSE in the human colon cancer cell line LoVo was further evaluated. The major saponins present in PNSE were ginsenosides Rg1 (31.1%) and Rb1 (34.4%), and the total content of the eight saponins identified (notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, and Rd, and isomeric ginsenosides Rb2 and Rb3) was 81.7%, indicating that it was a highly purified standardized saponin extract. Furthermore, PNSE was found to have a markedly cytotoxic effect and antiproliferative activity against the LoVo cell line in a dose- and time-dependent manner. Flow cytometry analysis demonstrated that PNSE caused cell cycle arrest at S phase. Moreover, PNSE was found to possess antioxidative capacities in the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and hydroxyl radical scavenging assay in vitro. Taken together, the present results suggest that naturally occurring PNSE may provide significant natural defense against human colon cancer. PMID:22316295
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.16... popcorn....
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.16... popcorn....
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.16... popcorn....
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.16... popcorn....
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.16... popcorn....
DNA signals at isoform promoters
Dai, Zhiming; Xiong, Yuanyan; Dai, Xianhua
Transcriptional heterogeneity is extensive in the genome, and most genes express variable transcript isoforms. However, whether variable transcript isoforms of one gene are regulated by common promoter elements remain to be elucidated. Here, we investigated whether isoform promoters of one gene have separated DNA signals for transcription and translation initiation. We found that TATA box and nucleosome-disfavored DNA sequences are prevalent in distinct transcript isoform promoters of one gene. These DNA signals are conserved among species. Transcript isoform has a RNA-determined unstructured region around its start site. We found that these DNA/RNA features facilitate isoform transcription and translation. These results suggest a DNA-encoded mechanism by which transcript isoform is generated. PMID:27353836
DNA signals at isoform promoters.
Dai, Zhiming; Xiong, Yuanyan; Dai, Xianhua
Transcriptional heterogeneity is extensive in the genome, and most genes express variable transcript isoforms. However, whether variable transcript isoforms of one gene are regulated by common promoter elements remain to be elucidated. Here, we investigated whether isoform promoters of one gene have separated DNA signals for transcription and translation initiation. We found that TATA box and nucleosome-disfavored DNA sequences are prevalent in distinct transcript isoform promoters of one gene. These DNA signals are conserved among species. Transcript isoform has a RNA-determined unstructured region around its start site. We found that these DNA/RNA features facilitate isoform transcription and translation. These results suggest a DNA-encoded mechanism by which transcript isoform is generated. PMID:27353836
AAHD's Health Promotion and Wellness, Part 2: Health Promotion Programs
ERIC Educational Resources Information Center
Exceptional Parent, 2011
This article is part 2 of a 4-part series on "Health Promotion and Wellness" from the American Association on Health and Disability (AAHD). According to the U.S. Census Bureau, more than 54 million people--one in five Americans--have a disability, and these Americans are more likely to report: (1) Being in poorer overall health; (2) Having less…
21 CFR 601.94 - Promotional materials.
Code of Federal Regulations, 2011 CFR
... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
21 CFR 601.45 - Promotional materials.
Code of Federal Regulations, 2011 CFR
... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...
21 CFR 601.94 - Promotional materials.
Code of Federal Regulations, 2014 CFR
... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
21 CFR 601.45 - Promotional materials.
Code of Federal Regulations, 2014 CFR
... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
21 CFR 601.94 - Promotional materials.
Code of Federal Regulations, 2013 CFR
... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
21 CFR 601.45 - Promotional materials.
Code of Federal Regulations, 2013 CFR
... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...
Code of Federal Regulations, 2010 CFR
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1216.23 Section 1216.23 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion....
Compulsory Autonomy-Promoting Education
ERIC Educational Resources Information Center
Schinkel, Anders
Today, many liberal philosophers of education worry that certain kinds of education may frustrate the development of personal autonomy, with negative consequences for the individuals concerned, the liberal state, or both. Autonomy liberals hold not only that we should promote the development of autonomy in children, but also that this aim should…
When Promoting Democracy Is Counterproductive
ERIC Educational Resources Information Center
Esfandiari, Haleh; Litwak, Robert S.
The United States has begun a $75-million program to promote democracy by supporting Iranian nongovernmental organizations (NGOs). That program, coupled with loose talk about regime change from members of Congress, commentators close to the administration, and individuals within the administration, has fed a sense of vulnerability and paranoia…
Health Promotion: A Resource Book.
ERIC Educational Resources Information Center
Anderson, Robert, Ed.; Kickbusch, Ilona, Ed.
Health promotion redirects thinking about health by: reasserting its social and political aspects; ensuring the people the power to define their own health concerns; and placing health more clearly in the context of other aims in life. This compilation of 41 articles in 8 sections attempts to document this process of redirection of thought. The…
ERIC Educational Resources Information Center
Shum, Brenda
Data plays a starring role in promoting educational equity, and data-driven decision making begins with good state policies. With the recent passage of the Every Student Succeeds Act (ESSA) and a proposed federal rule to address racial disproportionality in special education, states will shoulder increased responsibility for eliminating…
Promoting Metacognition in Music Classes
ERIC Educational Resources Information Center
Benton, Carol W.
Metacognition is a type of thinking in which learners think about their own cognitive processes. Because it transcends disciplines and grade levels, metacognition is useful in many educational settings and can be transferred from the music classroom to other subject areas. Music educators can promote metacognition by designing and implementing…
Promoting Community Cohesion in England
ERIC Educational Resources Information Center
Morris, Andrew B.; McDaid, Maggie; Potter, Hugh
Following serious disturbances in some northern cities in England in 2001, concerns about possible rising inter-communal tension have led to a statutory duty to promote community cohesion being placed on schools. Inspectors from the Office for Standards in Education (Ofsted) are required to make judgements in the leadership and management section…
Promoting local management in groundwater
NASA Astrophysics Data System (ADS)
van Steenbergen, Frank
There is a strong case for making greater effort to promote local groundwater management—in addition to other measures that regulate groundwater use. Though scattered, there are several examples—from India, Pakistan, Yemen and Egypt—where groundwater users effectively self-imposed restrictions on the use of groundwater. There are a number of recurrent themes in such spontaneously-developed examples of local regulation: the importance of not excluding potential users; the importance of simple, low transaction cost rules; the power of correct and accessible hydrogeological information; the possibility of making more use of demand and supply management strategies; and the important supportive role of local governments. The case is made, using examples, for actively promoting local groundwater management as an important element in balancing groundwater uses. Two programmes for promoting local groundwater management in South India are described—one focussing on participatory hydrological monitoring, and one focussing on micro-resource planning and training. In both cases the response was very positive and the conclusion is that promoting local groundwater regulation is not difficult, costly or sensitive and can reach the necessary scale quickly.
Promoting Effective Communications with Paraeducators.
ERIC Educational Resources Information Center
Pickett, Anna Lou; And Others
This conference presentation on promoting effective communications with paraeducators working in special education consists of 13 distinct text items. The items deal with: (1) definition of paraeducators and the roles of teachers in working with paraeducators in inclusive classrooms; (2) the importance of teacher-paraeducator communication; (3)…
Promoting Diversity in Academic Leadership
ERIC Educational Resources Information Center
Page, Oscar C.
The challenge every college, university, and state higher education coordinating board has is changing demographics. In most states, minorities are becoming majorities, and the importance of gaining an understanding of other cultures becomes much more evident. To promote diversity in academic leadership, educators must recognize that the college…
Promoting Intellectual Growth in Adulthood.
ERIC Educational Resources Information Center
Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M; McLoughlin, Caven S.
Article discusses problems associated with promoting intellectual growth in adulthood. Defines characteristics of intelligent behavior as incorporating individual attainment of Resources, Intimacy, Competence, and Health (RICH). Presents the RICH theory as a way to define and address the goals of intelligent enhancement. (JDM)
Advertising and Sales Promotion Guide.
ERIC Educational Resources Information Center
North Carolina State Dept. of Public Instruction, Raleigh. Div. of Vocational Education.
This document contains teacher materials for a 4-unit, 1-year marketing education course in advertising and sales promotion offered in grades 11 and 12 in North Carolina. The preface contains a rationale for the development of the course, a course description, course objectives, a list of the instructional units of the course, and a list of the…
Promoting a Lifetime of Inclusion.
ERIC Educational Resources Information Center
Renzaglia, Adelle; Karvonen, Meagan; Drasgow, Erik; Stoxen, Craig C.
Discussion of ways to promote inclusion for individuals with severe disabilities first establishes the principle of normalization, then describes conditions and practices that reflect this principle and foster inclusion across the life span. These include universal design, person-centered planning, self-determination, and positive behavior…
Mutual Benefits in Promoting Bequests.
ERIC Educational Resources Information Center
Patterson, Charles W., III
Encouragement of wills and bequests is the backbone of a good planned giving program. Methods of promotion, types of will gifts, tax aspects, identification of potential donors, a simple bequest program, program evaluation, and the need for continuity and patience are discussed. (MLW)
University Festival Promotes STEM Education
ERIC Educational Resources Information Center
Quagliata, Andrew B.
STEM education is argued as an essential ingredient in preparing our children for careers of the future. This study describes a university festival that includes the promotion of STEM-related career interests in young people among its goals. A total of 203 participants between the age of 7 and 17 completed both pre-event and post-event surveys. In…
Promoting Discussions in ESL Students
ERIC Educational Resources Information Center
Navarro, Ann
Background: Teachers who work with English as a Second Language (ESL) students, struggle with promoting discussion during guided reading. When ESL students are asked comprehension questions during group discussions and throughout the reading of a book, often teachers receive minimal feedback. Purpose: The purpose of this research is to identify…
NASA Astrophysics Data System (ADS)
Penny, Alan
MEETING REPORT What does the UK presently do in the search for extraterrestrial intelligence and what are the plans for the future? Alan Penny reports on a meeting of UK academics active in SETI, held as sessions in the recent National Astronomy Meeting in Scotland - and the formation of the UK SETI Research Network to promote UK academic work.
Promoting and Assessing Mathematical Generalising
ERIC Educational Resources Information Center
Hill, Tiffany; Lannin, John; van Garderen, Delinda
Helping students generalise mathematical ideas is an essential component of teaching and learning of mathematics (Lannin, Ellis, Elliott & Zbiek, 2011). However, it can be challenging for primary teachers to assess and promote generalisation. Because generalisation is an essential part of mathematics instruction, the authors highlight the…
Promoting Education among TANF Teens.
ERIC Educational Resources Information Center
Cohen, Marie
This document examines issues related to promoting education among teenage recipients of Temporary Assistance for Needy Families (TANF). The document begins with background information about the provisions of recent federal legislation affecting TANF recipients under age 20. The following are among the 16 policy and management issues considered in…
Drugs that promote dental caries.
Dental caries result from erosion of tooth enamel or cementum by acidic substances produced by bacteria found in dental plaque. Caries can lead to pulp necrosis and tooth loss. Risk factors include certain dietary habits, poor oral hygiene, and dry mouth. Diabetes and Sjogren's syndrome can also promote dental caries. Psychotropic substances such as cocaine, methamphetamine, heroin and cannabis can promote dental caries. Many medicinal drugs facilitate the formation of dental caries, through various mechanisms; they include formulations with a high sugar content; drugs that cause dry mouth (especially antimuscarinics); drugs that lower the buccal pH (inhaled powders, etc.); and drugs that cause demineralisation (tetracyclines, etc.). In practice, patients (and parents) should be informed that some drugs can increase the risk of dental caries. They should be encouraged to adapt and reinforce dental hygiene, and advised to visit a dentist regularly. PMID:25802916
Electrochemical promotion of catalytic reactions
NASA Astrophysics Data System (ADS)
Imbihl, R.
The electrochemical promotion of heterogeneously catalyzed reactions (EPOC) became feasible through the use of porous metal electrodes interfaced to a solid electrolyte. With the O 2- conducting yttrium stabilized zirconia (YSZ), the Na + conducting β″-Al 2O 3 (β-alumina), and several other types of solid electrolytes the EPOC effect has been demonstrated for about 100 reaction systems in studies conducted mainly in the mbar range. Surface science investigations showed that the physical basis for the EPOC effect lies in the electrochemically induced spillover of oxygen and alkali metal, respectively, onto the surface of the metal electrodes. For the catalytic promotion effect general concepts and mechanistic schemes were proposed but these concepts and schemes are largely speculative. Applying surface analytical tools to EPOC systems the proposed mechanistic schemes can be verified or invalidated. This report summarizes the progress which has been achieved in the mechanistic understanding of the EPOC effect.
Promoting the exotic pet practice.
Harris, Don J
The marketing and promotion of an exotic pet veterinary practice allows the use of strategies that are not necessarily available in other veterinary disciplines. The advantage that an exotics practice enjoys is that it is able to capitalize not only on the unique nature of the species being attended but also on the specialized features of the hospital itself that make it specifically appropriate in caring for exotic pets. Before marketing, however, comes the responsibility that the practice live up to the claims made in promotional materials. A practice cannot ethically be presented as an "exotics" practice if it is nothing more than a dog and cat facility that is willing to attend to exotic pets. It is the competence of the veterinary staff and the appropriateness of the facility that determines the suitability of the practice for exotics management. PMID:16129354
Engineered Promoters for Potent Transient Overexpression
Ideses, Diana; Tikotzki, Ravid; Shir-Shapira, Hila; Shefi, Orit; Juven-Gershon, Tamar
The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3), which combines four core promoter elements (the TATA box, Inr, MTE and DPE) into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods. PMID:26872062
South Asia's health promotion kaleidoscope.
Mukhopadhyay, Alok
South Asia has 22 percent of the world's population but only 1.3 percent of the global income. Consequently 40 percent of the population is living in absolute poverty. However the health transition in some of its countries including India and Sri Lanka is a testimony to the fact that there are proven solutions to the problems of health and development within the region. The countries of the region have much in common, including a democratic political system, four major religions, a vibrant and living tradition of voluntarism and an extensive health infrastructure which is operating well below par. Despite the underlying unity, South Asia enjoys enormous cultural, linguistic and ethnic diversity. In this large, complex and vibrant region, health promotion is a challenging task, but it also holds the key to a dramatic change in the global health situation. Many of these solutions lie in wider areas of socio-political action. There are much needed shifts in the health promotion and development efforts, particularly in the area of poverty and social justice; gender inequity; population stabilisation; health and environment; control of communicable and non-communicable diseases; and urban health strategies. The principle of cooperation, partnership and intersectoral collaboration for health will be explored. Developing an appropriate, sustainable and people centred health and development strategy in the coming decades is an enormous challenge. There has been an attempt to focus on the emerging needs of the region, which call for health promotion, and involvement of civil society, private sector and the governments bestowed with the increased responsibility of ensuring health security for people. Strengthening the existing health systems, allocating adequate resources for health development and ensuring community participation are all prerequisites to the success of health promotion in the region. PMID:18372876
Promoting physical activity in schools.
Armstrong, N
Neil Armstrong, director of the Coronary Prevention in Children Project, argues for a comprehensive programme for promoting children's physical activity. The project's survey of adult coronary risk factors in British children revealed a worryingly low level of physical activity among British schoolchildren. Schools are ideally placed to encourage children to take physical exercise, he writes, but parental role models also play an important part. PMID:8244725
[Health promotion and communication strategy].
Moreau, D
This article presents a brief overview of the evolution of knowledge in health communication. Theorists suggest interesting solutions to improve messages related to health, but practitioners are asking for the means to put them to use. In health communication, then, efforts must be made to apply theory to practice. Nurses, working with other professionals, should be encouraged to engage in research aimed at improving communication strategies in health promotion. Interdisciplinary co-operation is key. PMID:11143661
Incentives to promote family planning
Heil, Sarah H.; Gaalema, Diann E.; Herrmann, Evan S.
Objective Over the past 60 years, population control has become an increasingly urgent issue worldwide as a growing population strains already limited resources. The use of financial incentives to promote family planning is an innovative approach that has potential to make a contribution to efforts to better manage population growth. This report reviews eight studies that examined the effect of incentives on family planning. Method Published studies that tested the impact of incentives to promote some aspect of family planning and included an appropriate control or comparison condition were reviewed. Results Incentives have been used to promote attendance at contraceptive education sessions, adoption and continuation of contraceptive methods, sterilization, and to limit family size. All but one of the eight studies reviewed reported positive outcomes, but weaknesses in study design and execution limit the strength of the conclusions that can be drawn. Conclusion Review of this literature suggests that family planning behaviors, like other behaviors, are sensitive to incentives. Given the tremendous need for efficacious interventions in global efforts to manage population growth, further research on this topic using more rigorous experimental methods is warranted. PMID:22743293
Physical characteristics in eucaryotic promoters.
Bensimhon, M; Gabarro-Arpa, J; Ehrlich, R; Reiss, C
For a series of wild type and mutated eucaryotic gene prelude sequences (mainly "promoters" of SV40 early gene (Benoist and Chambon, Nature 290, 304 (1981); Moreau et al., Nuc. Acids Res. 9, 6047 (1982)) and of Herpes Simplex Virus TK gene (McKnight and Kingsbury, Science 217, 316 (1982)), in vivo promoter activity and local stability (denaturability) have been correlated. In agreement with the conclusions drawn in these papers, the correlation points to three major eucaryotic promoter elements and loci: (i) enzyme enabling by an enhancer sequence; SV40 and Moloney Sarcoma Virus enhancers have a striking stability homology; (ii) enzyme activation, occurring 50-70 b.p. upstream the cap site in a high stability domain; the enzyme apparently deactivates exponentially upon moving away to trap site; (iii) enzyme positioning at trap site, 30 +/- 5 b.p. upstream the cap site. The trap site contains the TATA box, or, when absent, other low stability domains downstream the activator. The number and occupancy of cap sites may depend on the stability and size of the trap site-cap site couple and its distance from the activator. PMID:6306592
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....
Promoting Racial Equality in the Nursing Curriculum.
ERIC Educational Resources Information Center
Foolchand, M. K.
Equality in nursing education and the profession can be promoted in the following ways: a working policy on racism and equal opportunities; curriculum content that explores stereotypes, values, attitudes, and prejudices; and multicultural health research, education, and promotion. (SK)
Promoting spiritual health in home healthcare.
Taylor, Elizabeth Johnston
This article explores how clinicians can promote patient and family caregiver spiritual health. After a review of pertinent theory and research, clinical implications are identified, including appropriate goals for clinicians with regard to spiritual health promotion. PMID:18562823
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...
Health promotion capacity mapping: the Korean situation.
Nam, Eun Woo; Engelhardt, Katrin
Ten years ago the Republic of Korea enacted the National Health Promotion Act, setting the stage for health promotion action in the country. A National Health Promotion Fund was established, financed through tobacco taxes, which is now one of the largest in the world. However, despite abundant financial resources, the infrastructure needed to plan, implement, coordinate and evaluate health promotion efforts is still underdeveloped. Currently, health promotion capacity mapping efforts are emerging in Korea. Two international capacity mapping tools have been used to assess the Korean situation, namely HP-Source and the Health Promotion Capacity Profile, which was developed prior to the sixth Global Conference of Health Promotion, held in August 2005 in Bangkok, Thailand. The article summarizes and discusses the results of the capacity mapping exercise, highlights its challenges and suggest ways to improve the accuracy of health promotion capacity mapping. PMID:17341492
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions... raspberries to the general public and the food industry for the purpose of improving the competitive...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions... raspberries to the general public and the food industry for the purpose of improving the competitive...
Nodal Promotes Glioblastoma Cell Growth
De Silva, Tanya; Ye, Gang; Liang, Yao-Yun; Fu, Guodong; Xu, Guoxiong; Peng, Chun
Nodal is a member of the transforming growth factor-β (TGF-β) superfamily that plays critical roles during embryogenesis. Recent studies in ovarian, breast, prostate, and skin cancer cells suggest that Nodal also regulates cell proliferation, apoptosis, and invasion in cancer cells. However, it appears to exert both tumor-suppressing and tumor-promoting effects, depending on the cell type. To further understand the role of Nodal in tumorigenesis, we examined the effect of Nodal in glioblastoma cell growth and spheroid formation using U87 cell line. Treatment of U87 with recombinant Nodal significantly increased U87 cell growth. In U87 cells stably transfected with the plasmid encoding Nodal, Smad2 phosphorylation was strongly induced and cell growth was significantly enhanced. Overexpression of Nodal also resulted in tight spheroid formation. On the other hand, the cells stably transfected with Nodal siRNA formed loose spheroids. Nodal is known to signal through activin receptor-like kinase 4 (ALK4) and ALK7 and the Smad2/3 pathway. To determine which receptor and Smad mediate the growth promoting effect of Nodal, we transfected siRNAs targeting ALK4, ALK7, Smad2, or Smad3 into Nodal-overexpressing cells and observed that cell growth was significantly inhibited by ALK4, ALK7, and Smad3 siRNAs. Taken together, these findings suggest that Nodal may have tumor-promoting effects on glioblastoma cells and these effects are mediated by ALK4, ALK7, and Smad3. PMID:22645523
Natural Selection Promotes Antigenic Evolvability
Graves, Christopher J.; Ros, Vera I. D.; Stevenson, Brian; Sniegowski, Paul D.; Brisson, Dustin
The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections
Health promotion through forgiveness intervention.
Recine, Ann C; Stehle Werner, Joan; Recine, Louis
The purpose of this article is to offer evidence-based forgiveness interventions clinically useful to nurses in holistic health promotion for individuals, families, and communities. Forgiveness interventions are developed and described within four approaches inspired by midrange nursing theorists who have adapted their theories from Bandura's Social Learning Theory and Frankl's Theory of Meaning. Interventions are also assimilated from a comprehensive review of theoretical and research literature. The four interventional approaches include persuasive information, vicarious experience, awareness of physiological reactions, and enactive attainment. Barriers to implementation are discussed as well as ways to individualize the interventions. PMID:19182268
Immune cell promotion of metastasis
Kitamura, Takanori; Qian, Bin-Zhi; Pollard, Jeffrey W.
Metastatic disease is the major cause of death from cancer, and immunotherapy and chemotherapy have had limited success in reversing its progression. Data from mouse models suggest that the recruitment of immunosuppressive cells to tumours protects metastatic cancer cells from surveillance by killer cells, which nullifies the effects of immunotherapy and thus establishes metastasis. Furthermore, in most cases, tumour-infiltrating immune cells differentiate into cells that promote each step of the metastatic cascade and thus are novel targets for therapy. In this Review, we describe how tumour-infiltrating immune cells contribute to the metastatic cascade and we discuss potential therapeutic strategies to target these cells. PMID:25614318
Nonpharmacologic techniques for promoting sleep.
Cole, Roger J
Athletes could benefit from simple, self-administered, nonpharmacologic techniques for promoting sleep onset. A wealth of physiologic evidence and limited clinical data support several potential methods that might be conveniently applied at or near bedtime. These include inverted posture, skin warming/core cooling, motor relaxation, sensory withdrawal/masking, breathing techniques, and cognitive relaxation. Each holds promise as a possible element of a comprehensive sleep management program, but all need further investigation to confirm their efficacy or to determine optimal methods of application. PMID:15892928
Code of Federal Regulations, 2012 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...
Code of Federal Regulations, 2013 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...
Code of Federal Regulations, 2014 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...
Code of Federal Regulations, 2011 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...
Code of Federal Regulations, 2010 CFR
... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...