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Summary of Gynostemma pentaphyllum
Primary Information, Benefits, Effects, and Important Facts
Gynostemma Pentaphyllum is a plant which is sometimes referred to as either 'Southern Ginseng' or 'Cheap Ginseng' as it was used as a cheap substitute for Panax Ginseng (as aside from Codonopsis Pilosula, which was used as an adulterant for Panax Ginseng to sell it at the normal price but cut costs). Surprisingly, Gynostemma has a good content of Ginsenosides that were once thought to be wholly unique to Panax Ginseng. As such, the biological effects of Gynostemma and Panax seem to be quite similar except Gynostemma may be more anti-diabetic (due to the unique Gypenosides in Gynostemma, that are not in Panax).
There are limited human studies at the moment, as most studies are attempting to delineate the large amount of Gypenosides in this herb to see which ones can be seen as the 'active' compounds. Currently, we have two human studies suggesting that a tea made from Gynostemma can be used alongside standard anti-diabetic therapy and augment the efficacy of it over time (known as adjunct therapy).
Most of its 'beneficial' effects beyond the diabetic effects (which are mediated by a possible mix of AMPK activation and PTP1B inhibition; the amount each contributes to the overall effects unknown) come from inducing antioxidant enzymes and protecting cells from oxidative damage over time. There seems to be a motif where preloading and chronic loading is very protective at low doses, and acute supplementation or rehabilitation (taking the supplement after the stressor) appears to be less effective. As such, the health effects of Gynostemma Pentaphyllum appear to be more prophylactic rather than rehabilitative or therapeutic.
This herb is also touted for youthfulness and longevity, but neither claim has been explored. Additionally, the anti-cancer effects are still in beginning stages of research but the effects appear to be very similar in many cell lines; some compound in the Gypenoside fragment may be an inducer of p53, a tumor suppressor gene, as the downstream events associated with p53 activity have been noted repeatedly (although direct kinetics between Gypenosides and p53 have not yet been investigated; this is a likely theory but not established)
Overall, this is a more anti-diabetic Panax Ginseng; the downside is that the other benefits associated with Panax Ginseng (adaptogenic, cognitive enhancing, anti-fatigue) have not yet been assessed properly with Gynostemma Pentaphyllum.
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Things To Know & Note
Other Functions:
Primary Function:
Also Known As
Southern Ginseng, Jiao Gu-lan, Giao-Co-Lam (Tea), jiaogulan
Goes Well With
Grape Seed Extract (for alleviating central insulin resistance)
Caution NoticeExamine.com Medical Disclaimer
Has not yet been tested for drug-drug interactions in regards to P450 enzymes
How to Take Gynostemma pentaphyllum
Recommended dosage, active amounts, other details
Although not too many trials have been conducted, the two studies noting that Gynostemma Pentaphyllum could be useful to help diabetes used 6g of the leaves (dry weight) and made tea from that. The leaves themselves are a good source of both classes of active ingredients (the saponins, of which Gypenosides are a subset, and the flavonoids), and this is currently the best known dosage to use.
Alternatively, due to the similarity between Gynostemma pentaphyllum gypenosides and Panax ginseng ginsenosides they may have a similar active level for isolated alkaloids. 100-500mg gypenosides may be a good educated guess to start from.
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Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects gynostemma pentaphyllum has on your body, and how strong these effects are.
|Level of Evidence [show legend]
|Robust research conducted with repeated double-blind clinical trials
|Multiple studies where at least two are double-blind and placebo controlled
|Single double-blind study or multiple cohort studies
|Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
|Very High See 2 studies
Decrease in blood glucose in diabetics given gynostemma tea or root appears to be greater than other supplements; currently no studies in otherwise healthy persons.
|Very High See 2 studies
Preliminary evidence in diabetics suggest potent HbA1c reducing effects (6g of the root reducing HbA1c by 2% over a few months)
|Very High See 2 studies
An improvement in insulin sensitivity is noted in diabetics which is fairly notable; no studies in otherwise healthy persons at this time
|- See study
A decrease in fasting insulin has been noted with supplementation in diabetics
|- See study
Liver enzymes in a model of fatty liver are decreased with gynostemma ingestion
|- See study
Long term, but not short term, ingestion of gynostemma tea appears to reduce fat mass in diabetics; no studies in healthy persons yet
|- See study
HDL appears unaffected
|- See study
LDL cholesterol appears unaffected
|- See study
No significant alterations in triglycerides noted with supplementation
|- See study
No significant influences on uric acid
Studies Excluded from Consideration
Safety study[1]
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Research Breakdown on Gynostemma pentaphyllum
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Gynostemma pentaphyllum (Southern Ginseng) of the Cucurbitaceae family is a plant that has usage in Traditional Chinese Medicine (where it is referred to as Jiao Gu-lan) for cough, wheeze, chronic bronchitis and infectious hepatitis. It seems to possess ginsenoside-like saponins despite not being related to Panax Ginseng (True Ginseng),[2] and tea that contains higher level of Panax's ginsenosides are sweeter (which make it fairly popular).[3] It is considered a longevity herb[4] with herbs in the Gynostemma genus referred to as herbs of immortality.[5][6]
A herb that itself has a traditional use mostly as a tea, it has sometimes been called 'Cheap Ginseng' since it has many of the same effects and was cheaper (Panax Ginseng has a history where the supply was sequestered by the upper classes, which raised the market value)
The main Gypenoside class of bioactives (those unique to Gynostemma Pentaphyllum) include:
Gylongiposide I[7]
Gypenbiosides A and B[9]
Gypenosides GC1 to GC7 (2α,3β,12β,20(S)-dammarane type structure)[10]
Gypenoside III at 0.9% dry weight (a glycoside of Ginsenoside Rb1), IV (a glycoside of Ginsenoside Rb3), VIII at 0.4% (Ginsenoside Rd), XII (Ginsenoside F2)[11][12][13]
Malonyl Gypenosides III and VIII (Malonyl Ginsenosides Rb1 and Rd, respectively)[11]
Gypenoside LXXIV (G74),[14] Gypenoside XLIX, and Gypenoside A (XLIII)[15]
Gymnemaside VI[10]
Gynostemosides A-E (Megastigmane compounds based on the backbone of 3,4-dihydroxy-5,6-dihydro-β-ionol)[16]
Gynoside A, ocotillone type triterpenoid ((20S,24S)-20,24-epoxy-12,25-dihydroxy-dammaran-3-yl-O-β-D-glucopyranosyl(1→2)-β-D-xylopyranoside)[17] as well as B-E[18]
Phanoside, a term used to refer to four isomers of a Gypenosapogenin glycoside[19][20]
Gypenosides are Gypenosapogenin or Ginsenoside structures (the former pictured below) attached to sugars; as such, they are Gypenosapogenin or Ginsenoside Glycosides (Glycoside merely being a term to refer to 'attached to sugar(s)'; a storage form of sorts)
With other notable saponin structures as:
Ginsenosides Rb1, Rb3, Rd and F2 (all found in Panax Ginseng)[3]
3β,20(S),21-trihydroxydammar-24-ene (aka. H6) with the glycoside of Gypenoside XLIX,[21] structurally related 3β,20ξ,21-trihydroxydammar-23-ene glycosides[22]
Damulin A and B, ranging from 0.09-0.1% dry weight and increasing up to 0.7-0.9% when heat treated (autoclaving at 121°C);[23] a heat treated extract with high Damulin content being called 'Actiponin'.[23] The true names of these compounds being diglycosides of 2α,3β,12β–trihydroxydammar-20(22)-E,24-diene and 2α,3β,12β-trihydroxydammar-20,24-diene, respectively[24]
(20S)-dammarane-24(25)-ene-3β,20,21-tetrol and (20S,24S)-dammarane-25(26)-ene-3β,12β,20,24-tetrol[8]
Dammarane-(E)-20(22)-ene-3β,12β,25-triol and 20(S)-dammarane-25(26)-ene-3β,12β,20-triol[8]
(23S)-3β-dihydroxyl-dammarane-4-ene-21-oic acid-21, 23-lactone[8] (also found in Machilus yaoshansis[25])
(20S,23S)-3β,20-dihydroxyldammarane-24-ene-21-oic acid-21, 23-lactone (and its R,R enantiomer)[8]
3β-hydroxyetio-17β-dammaranic acid[8]
Some saponins in Gynostemma Pentaphyllum are literally the same Ginsenosides found in Panax Ginseng, with other saponins being more generalized among herbs
And various other non-saponin compounds:
Carotenoids (cis-neoxanthin, violaxanthin, auoxanthin, luteoxanthin, lutein, α-carotene and β-carotene)[26]
Chlorophyll compounds (Chlorophyll A (113.8ug/g) A'(11.0ug/g) B (287.9ug/g) and B'(11.1ug/g), Pheophytin A (2508.3ug/g) A'(111.2ug/g) B(319.6ug/g) B'(13.2ug/g); hydroxy derivatives including hydroxypheophytin A (88.6ug/g) A'(66.5ug/g) B(11.2ug/g) B'(8.5ug/g) and hydroxychlorophyll A (23.8ug/g) and B (15.0ug/g)[26][27] as well as pyropheophytin A (76.0ug/g)[27]
Ombuine (Ombuin-3-O-β-D-glucopyranoside)[28]
Caffeic Acid[29]
Quercetin as di(rhamno)-hexoside (548.3mcg/g) and rhamnohexoside (1249.6mcg/g)[29][30] and in the leaves of diploids (9.64-12.1mg/g) and tetraploids (0.82-1.27mg/g)[31]
Kaempferol as rhamno-hexoside (1792.9-2416.5mcg/g), 3-O-rutinoside (429.7mcg/g), and free form.[29][30] Kaempferol 3-O-di-p-coumaroylhexoside has also been detected[31]
Rutin (1602.8mcg/g)[30][29] and in the leaves in the range of 18.97-23.03mg/g for diploid samples and 9.74-11.19mg/g for tetraploid[31]
3,5,3′-trihydroxy-7,4′-dimethoxyflavone (From the leaves)[4]
Selenium ranging from 0.094-0.265mg/kg, with one outlier at 1.730[32]
Some trace minerals[33]
With some bioactive polysaccharides:
PGSP at 1.5% dry weight; water-soluble and a structure of glucose:galactose:arabinose:rhamnose:galacturonic acid:xylose:mannose:glucuronic acid in a 23.2:18.9:10.5:7.7:4.7:3.9:3.1:1.2 ratio[35]
In general, ethanolic root extracts are concentrated for saponin and triterpenoid structures (first two subsections) while hot water extracts of the leaves (teas) are concentrated for flavonoids; there will still be flavonoids in the roots and saponins in the leaves though; the polysaccharides are in the root mostly and confer a caloric content as they are carbohydrates
When assessing overall quantities of molecule classes, saponins have been found in the range of 64.57-132.6mg/g (6.4-13.2% Saponins wet weight) which are concentrated in ethanolic extracts.[32] Of these, 2.4% (total weight of all parts) are dammarane-type saponins, with 75% of these dammarane-type saponins belonging to the class of Gypenosides (so effectively, Gynostemma Pentaphyllum is around 2% Gypenosides by weight if not otherwise concentrated).[15] Unlike most saponin-containing plants, the leaves appear to confer the highest concentration of saponins with the roots being lowest (stem intermediate).[36]
The whole plant of Southern Ginseng has been found to reverse Multidrug Resistance, where P-Glycoprotein resistance to colchine (no effect on vinblastine or taxol) was reversed approximately 15-fold in vitro in the presence of 0.1mg/mL total Gypenosides, which was increased to 42-fold when purified further effectively abolishing the resistance.[37] A later study isolated 3β,20(S),21-trihydroxydammar-24-ene (dubbed H6) found that while it did not exert toxicity below 50uM, lower concentrations were able to augment Vincristine-induced cytotoxicity, reducing the IC50 of Vincristine when H6 was at 5-20uM to the range of 2-9% of Vincristine alone.[21] Additionally, this study suggested that H6 may induce P-gp (via ATPase) and inhibit MRP1 (via STAT3 inhibition) in KB/VCR cells.[21]
Appears to interact with a drug efflux protein potently, and may have a role in augmenting some chemotherapies. The practical significance of this has not been tested in a living system yet
In cultured substantia nigra dopaminergic neurons (highly associated with the pathology of Parkinson's Disease), 1-methyl-4-phenylpyridinium ion (MPP+) induced damage is attenuated with Gypenosides at 50-200ug/mL, with more efficacy when pretreated rather than posttreated.[38] 200ug/mL was associated with almost normalization of anti-oxidant enzymes and pro-oxidative biomarkers (MDA, ROS) when pretreated.[38]
Protection against MPTP have been noted in vivo in rats associated with less oxidative damage,[39] and has been noted against hydroxydopamine (a pro-oxidative derivative of dopamine) following oral administration of 10-30mg/kg of the ethanolic extract of Gynostemma Pentaphyllum, where the cell survival that was reduced to 40.1% (relative to 100% of control) was attenuated to 67.4% and 75.8% at the two doses over 28 days (with a similar degree of preservation of catecholamines, which were reduced in toxin control).[40]
Appears to be protective of a cluster of neurons that are involved in Parkinson's Disease, with this protection likely mediated via anti-oxidant effects (and more effective when pre-loaded). No human studies, but has shown efficacy in mice at relatively low doses
An in vitro study on hippocampal cells deprived of oxygen and glucose noted that an ethanolic extract of Gynostemma pentaphyllum appears to preserve evoked field potential amplitude almost wholly when preincubated for 120 minutes prior to experimentation with no protective effect if incubated 60 minutes prior to insult.[41] At 60ug/mL ethanolic extract, a two-fold induction of Superoxide Dismutase (SOD) protein content was noted with a 20% increase in glutathione peroxidase after 48 hours incubation; these changes were independent of changes in DCFH fluorescence or H2O2 concentration, suggesting the increase in anti-oxidant enzyme defense was independent of changes in the basal oxidative balance.[41] A near complete restoration of evoked field potentials can be achieved retroactively, but requires 240ug/mL to do so in vitro, thought to be due to direct antioxidant potential rather than induction of SOD.[42] Protective effects have also been noted in vitro in the range of 100-400mcg/mL Gypenosides against glutamate toxicity, thought to be secondary to an increase of γ-GCS and GR mRNA which attenuated glutathione depletion.[43]
May have protective effects secondary to inducing anti-oxidant enzymes, with both pretreatment and acute treatment being effective but a lower dose required if preloaded (possibly related to inducing anti-oxidant enzymes, rather than directly acting as an antioxidant)
In a model of rat cognitive impairment (BCCAO), rats injected with 100mg/kg or 200mg/kg Gynostemma Pentaphyllum for 61 days after surgery and assessed by a Morris water maze task (assessment of memory formation and retention) noted that only the higher dose was associated with improved memory formation following injury and was the only dose associated with improved Superoxide Dismutase (SOD), lipid peroxidation (MDA), and histological assessment.[44] Another study has induced BCCAO injury to rats but followed it up with oral ingestion of 200mg/kg or 400mg/kg concentrated Gypenoside (rather than the whole plant extract) for 33 days after injury and noted a somewhat attenuated adverse morphology on white matter of the brain associated with normalized SOD in the corpus callosum and optic tract with significantly attenuated 4-HNE and MDA.[45]
The particular Gypenoside known as TN-2 at doses of 10-40mg/kg was shown to inhibit scopolamine-induced learning deficits in the range of 40-96% with 20mg/kg being maximally effective.[46] There was no inhibitory effect on acetylcholinesterase (usually associated with improvements in scopolamine models), was equally effective as Tacrine as active control (10mg/kg) and was associated with an induction of CREB and BDNF in the hippocampus, the latter of which appeared to exceed the normal control group.[46] Similar protective effects have been noted with Gypenoside LXXIV.[14]
Protective effects have been noted at large concentrations of either oral or injected Gypenosides in animals, no human studies
Mechanistically, Gypenosides have once been shown to inhibit the Na(+),K(+)-ATPase enzyme in cardiac tissue in a reversible and concentration dependent manner between 10-300mcg/mL with an IC50 of 58.79+/-8.05mcg/mL (brain ATPase also inhibited with an IC50 of 52.07+/-6.25mcg/mL), and appeared to have less inhibitory potential when ATP concentrations were increased from 0.5mM to 5mM.[47] Gypenosides compete with sodium at the Na-binding site, causing a shift in ATP/Na-ATP equilibria and an increased affinity of ATPase for ATP, which overall established Gypenosides as counter competitors.[47] These effects may underlie how 2.5-10mg/kg (injections) of Gypensides (as well as injections of 0.7mg/kg Gypenoside III and 0.3mg/kg Gypenoside VIII) all exerted protection against toxin induced tachycardia and arrythmia; nearing the potency of Vermapril (1mg/kg) but slightly underperforming.[11]
May preserve heart contractility to a moderate degree
In diabetic rats suffering from cardiomyopathy (streptozotocin injected), oral ingestion of 100mg/kg Gypenosides which was ineffective in reducing blood glucose over 6 weeks was able to normalize left ventricular function (LVSP, LVEPD) by about 41-55% (100% being that of control levels, 0% diabetic control) without significantly affecting titin or nebulin content, two cytoskeletal proteins of the heart.[48] This was hypothesized to be either through antioxidant effects of modulating calcium channels, although neither claim was tested.[48] 100mg/kg appears to be more effective than 50mg/kg and 200mg/kg, suggesting an optimal dosage range.[49]
Appears to reduce the adverse effects of high serum glucose on cardiac tissue in rats
Gypenosides from Southern Ginseng appears to induce endothelial-dependent vasorelaxation that is blocked by L-NAME, thus is mediated via the NO-cGMP pathway.[50] In cultured endothelial cells, incubation with 50mcg/mL mixed Gypenosides increased Nitric Oxide levels to 435+/-38.2% of control which was augmented with addition of the A23187 calcium ionophore and attenuated with Indomethacin.[50]
It is possible that Gypenosides may induce nitric oxide, but this was an in vitro study and not in a living system
Gypenosides at 300mcg/mL may decrease VCAM-1 mRNA activity, and a further ethanolic extract with a higher concentration of Gypenoside XLIX was able to decrease this activity (induced by TNF-α) at 50mcg/mL but with an IC50 of 186.8uM and near normalization to control cultures at 300mcg/mL.[15] This was hypothesized to be due to PPARα agonistic abilities[15] (with then inhibit NF-kB, a locus of whose inhibition greatly reduced VCAM-1) and this PPARα agonistic property has been previously noted, the potency of which is not significantly different than Wy-14643 at similar concentrations (trending to be weaker).[51][52] This was confirmed when MK-886 (PPARα inhibitor) abolished the benefits of this Gypenoside.[15]
May reduce vascular adhesion factors via PPARa, which may indirectly reduce artherosclerosis via preventing immune cell adhesion to the arterial wall
A study in obese rats given 150-250mg/kg Gynostemma Pentaphyllum (90% Gypenosides) for 5 weeks. At 4 days after ingestion triglycerides were unaltered at 150mg/kg while reduced 36% with 250mg/kg, 2 weeks in triglycerides were reduced 27% with 150mg/kg and 33%; the degree of triglyceride reduction appeared to max at around 35% at 5 weeks in both groups.[53] Total cholesterol was reduced in the range of 13-22% with a decrease in LDL-C as well (HDL-C unaffected).[53]
There appeared to be improvements in postprandial triglycerides after 5 weeks of supplementation in response to a test meal with Gynostemma supplementation.[53] These hypolipidemic effects may also occur acutely, as one study using P407 (an inhibitor of lipoprotein lipase, which causes acute spikes in triglycerides) with a 4 day preload of Gypenosides at 250mg/kg was able to reduce the spike in triglycerides by 53% (total cholesterol by 10%, HDL unaffected) but more dramatic effects were noted after 14 days (85% attenuation of the P407-induced increase).[54] This was thought to be from attenuating the effects of P407 on the LPL enzyme, and Gypenosides in isolation had no effect on the LPL receptor between 5-100ug/mL.[54]
Appears to reduce circulating triglycerides over a prolonged period of time
A polysaccharide from Gynostemma appears to be able to bind to bile acids with a greater gram per gram affinity relative to psyllium fiber, which may underlie possible cholesterol reducing effects (currently unexplored).[55]
200mg/kg of Actiponin (heat treated Southern Ginseng with 0.96% Damulin A and 0.68% Damulin B) over 8 weeks was able to attenuate weight gain of genetically obese mice by 8.1% relative to control; with the active control of 30mg/kg Sibutramine reducing this weight gain 10% independent of any changes in food intake.[23] A later portion of this study gave 150mg/kg and 300mg/kg to adult obese mice and noted a 5.7% and 7.7% reduction in body weight independent of food intake; these effects were thought to be mediated via AMPK activation in skeletal muscle tissue.[23]
Two compounds are suspected to be fat burners via AMPK activation and this has been noted in a living system, although the degree of benefit with a standard oral serving of Gynostemma Pentapyllum with a lower Damulin content is not known
Gynostemma Pentaphyllum (90% Gypenosides) appears to have an IC50 of 42.8µg/mL against α-glucoside (which outperformed Arcabose at 53.9µg/mL).[53]
May be able to reduce carbohydrate absorption; no fecal tests conducted so the degree of this inhibition is not known
Saponins in general from Gynostemma Pentaphyllum appears to have inhibitory potential on the PTP1B enzyme (a negative regulator of insulin signalling[56] that is a therapeutic target of Type II diabetes management[57]) in a concentration dependent manner, including gypensapogenin A (IC50 23uM), B (IC50 24.5uM), E (IC50 13.1uM), and G (IC50 19.7uM) with less efficacy (IC50 49uM) from F and some from 3β-hydroxyetio-17β-dammaranic acid (24.5uM)[8] with most potency coming from (20S)-3β,20,23ξ-Trihydroxydammarane-24-en-21-oic acid-21,23 lactone with an IC50 of 5.3+/-0.4μM via competitive inhibition with a Ki of 2.8μM; comparable to the active controls of corosolic acid (IC50 7.5+/-0.6μM) and ursolic acid (3.6+/-0.2μM).[58]
These compounds have been structurally modified (into compounds not naturally occurring in Southern Ginseng) to more potent inhibitors due to their novel structures; with IC50 values as low as 0.27uM.[59]
Compounds in Southern Ginseng appear to be relatively effective inhibitors of PTP1B, which can help glucose uptake into cells by preserving the function of the insulin receptor. At least in regards to natural options, these appear to be moderately potent
A compound from Gynostemma Pentaphyllum known as Phanoside appears to be able to induce insulin secretion[20] which can occur in both normal and diabetic pancreatic tissue at low and high normal glucose concentrations in a concentration-dependent manner.[19] Mechanistically, it was found to not be inhibited by any added agent at low glucose concentrations, which may be related to facilitating insulin exocytosis (as many classical mechanisms of K-ATP channel closure, calcium influx, and PKA/PKC activity were found to be independent of Phanoside).[19]
One compound may increase insulin secretion, which paired with a protective effect on the pancreas (see the Pancreas section of "Interactions with Organ Systems") Gypenosides may be pro-insulinogenic depending on context
When looking at rat studies, usage of 100mg/kg of the Gypenosides for 9 weeks fails to significantly reduce serum glucose in a streptozotocin-induced diabetic model.[48] Another study in db/db mice using low dose (0.0025% Gypenosides by weight of the diet) or high dose (0.01%) compared to rosiglitazone (0.005%) over 5 weeks noted that high dose was able to reduce fasting glucose (13.2%) but underperformed relative to rosiglitazone (57%); all test groups significantly increased fasting insulin levels relative to diabetic control.[60] Higher doses (200-300mg/kg injections; 1500mg/kg of oral ingestion) have been shown to acutely reduce blood glucose.[61]
In drug naive diabetics who were given gliclazide for 4 weeks at 30mg and then divided into group, 6g of Gynostemma Pentaphyllum (18% Saponins) in two divided doses against placebo (actually green tea catechins) noted that treatment with GP further decreased blood glucose and HbA1c although the improvement in insulin sensitivity was not statistically significant.[62] A tea made from Gynostemma Pentaphyllum (6g of the leaves) has been tested in isolation without drug therapy but alongside standard diet and exercise advice (also given to placebo tea group) in Type II Diabetics, and the Southern Ginseng group appeared to provide greater benefit to fasting glucose (5-fold greater reduction than placebo; totalling a 3+/-1.8mmol/L drop), HbA1c (2% reduction; placebo 0.2%), and insulin sensitivity over a period of 12 weeks.[63]
One rat study suggest high doses can acutely reduce glucose, but the two human studies conducted suggest that a tea made from Gynostemma Pentaphyllum can be an effective adjunct therapy alongside other treatments such as drug or exercise intervention and augment the efficacy of those interventions
In myotubes, the two dammarane-type saponins known as Damulin A and B can activate AMPK in a concentration and time dependent manner and secondary to this increased glucose uptake 1.7-fold at 60ug/mL (of a solution containing 0.93% Damulin A and 0.68% Damulin B), increased GLUT4 mobilization and increased fatty acid oxidation (2.2-fold),[23] and the increase in beta-oxidation from 150uM Damulin A or 12uM Damulin B is comparable to 1mM AICAR and the glucose uptake of 150uM (but not 12uM Damulin B) was not significantly than different than 2mM Metformin (although trended to be less potent).[24] In feeding rats 150-300mg/kg of this mixture for 9 weeks, AMPK and ACC activity was enhanced in vivo in the soleus muscle.[23]
Appears to activate AMPK in skeletal muscle tissue, which has been noted to occur after oral administration to rats. This may underlie fat burning effects and perhaps some glucose/lipid reducing effects
One study administering a bioactive polysaccharide to mice named GPP1a was able to prolong exercise to fatigue and preserve glycogen content in exercised mice, which was associated with less oxidative markers (MDA);[34] this study is duplicated in Medline.[34]
Only one study in mice with an isolated polysaccharide shows promise; polysaccharide may not exist in non-caloric supplement capsules (although it should in tea, as it is water soluble)
In cultured mouse macrophages (J774A.1), mixed flavonoid extracts appear to have fairly weak suppressive effects on LPS-stimulated macrophages (when assessing cytokine release).[32] Similar suppressive effects are seen with the Gypenosides in RAW 264.7 macrophages where LPS-induced nitric oxide release is attenuated with an IC50 of 3.1+/-0.4ug/mL when pretreated before LPS, with 25mcg/mL being as potent as 10mcg/mL aminoguanidine; when added at a time similar to LPS induction, Gypenosides were weaker and reached maximal inhibition with 25mcg/mL at 47.3+/-0.1% (rather than absolute suppression seen with preincubation).[64] iNOS mRNA and protein content are reduced, and the mechanism is thought to be tied to NF-kB inhibition.[64]
Limited evidence, but Gypenosides and the flavonoids appear to be anti-inflammatory on immune cells
One polysaccharide (PSGP) has been noted to, following injections of 25-100mg/kg into mice and then having the macrophages removed after 8 hours, was able to induce macrophage activity with 100mg/kg being as effective as 0.2mg/kg LPS, and in vitro a concentration of 100mcg/mL being as effective as 0.2mg/mL LPS (with higher doses dose-dependently being more effective up to 400mcg/mL).[35]
A water soluble polysaccharide has been shown to be proinflammatory (immune booster)
Beyond the above mechanisms, Gynostemma Pentaphyllum may offer putative anti-oxidant protection in immune cells.[65]
A hot water extract of Gynostemma Pentaphyllum fed at either 1.75g/kg or 5g/kg bodyweight 5 days a week for 4 weeks noted that airway inflammation at both doses was not significantly different than control (all three groups significantly better than Ovalbumin control).[66] Similar effects have been noted within one week with 5g/kg, although in this study 1.75g/kg was ineffective.[67]
The increase in eosinophils in the lungs (+50% in Ovalbumin control) was significantly attenuated with both doses to a 16.18-22.54% with small dose dependence, with infiltration significantly reduced.[66]
Gynostemma Pentaphyllum can possibly be useful to prevent immune cell infiltration and hyperresponsiveness to allergins; would be useful to read the "Lung" section of "Interactions with Organ Systems" as Gynostemma may also be somewhat anti-asthmatic
10, 30, and 50mg/kg ethanolic extract of Southern Ginseng (for 7 days) prior to a 2 week stressor of electrical shocks has also noted that the stress reduced reduction in thymus and spleen weights were attenuated in a dose-dependent manner and Lymphocyte count somewhat preserved (48% preservation in the thymus, absolute preservation in the spleen with 50mg/kg only).[68] This study also noted preservation of TNF-α secretion in response to LPS, preservation of splenocytic proliferation, and T-cell cytotoxicity but IL-1β was seemingly unaffected.[68] Preservation of T-cell cytotoxicity and lymphocyte count as been noted with similar oral doses of Souther Ginseng in response to dexamethasone-induced immunosuppression in mice[69] and a preservation of lympocyte count has been noted against cadmium-induced lymphocyte decline.[70]
Appears to be able to attenuate immunosuppression induced by various agents (preventing the decline in immune cell count that would otherwise occur with stressors); an indirect immune support effect
Low dose injections of Gynostemma Pentaphyllum hot water extract can increase IgG2a[71] and T-cell proliferation in response to an antigen (in these studies, Concavalin-A) at 0.05-0.5mg/kg.[71][72]
In mice sensitized with Ovalbumin, administration of 1.75-5g/kg Gynostemma Pentaphyllum hot water extract for 4 weeks was able to attenuate the increase in IL-5 and TNF-α without affecting IL-6 or IL-13 alongside a decrease in antigen-specific IgG1 and IgE with no significant differences between groups; IFN-γ was not significantly affected.[66] This is noted within 7 days of 5g/kg treatment, but not 1.75g/kg[67] and usage of Gynostemma Pentaphyllum does not appeared to be associated with significant haemolytic activity when used as vaccine adjuvant where 200mcg Gypenosides induce more splenocyte proliferation than 200mcg Aluminum, but similar levels to that of 50-100mcg Quil-A (a saponin isolated from Quillaja saponaria with proven adjuvant properties).[73] This study noted that Gypenosides induced less IgG and IgG1 than Quil-A, but similar levels of IgG2b.[73]
Gypenosides may augment the body's antibody response to antigens, and act as an immune support agent. Limited evidence, however, but this effect is similar to that of Panax Ginseng
Oral ingestion of 50, 100, or 200mg/kg Gynostemma Pentaphyllum given to mice alongside a testicular toxin (10mcg zearalenone) was able to wholly preserve superoxide dismutase (SOD) concentrations in the lowest dose relative to 10% alcohol control and progressively induced SOD activity in a dose-dependent manner; MDA (indicative of lipid peroxidation) was also reduced at all doses.[74] Germ cell apoptosis was greatly attenuated in a dose-dependent manner and this was associated with an increase in Bcl-2 to Bax (the higher the ratio indicative of cell survival), and histological examination appeared normalized at the highest dose.[74]
Appears to be quite protective of germ cells, which although isn't a 'pro-fertility' mechanism may indirectly support fertility. A fairly potent anti-oxidant effect in the testicles
One study using low-dose Gynostemma (0.005-0.05% of the rat diet) in db/db mice that developed diabetes noted that despite lacklustre effects on lowering glucose (dose was too low for this effect) that serum insulin was markedly higher than the diabetic control (75-224%) and higher than Rosiglitazone active control (29-139%).[60] As assessed by histological examination, Gynostemma at these doses appeared to greatly preserve the islets of Langerhans and the insulin-secreting β-cells that were perturbed during diabetic pathology.[60]
Low doses show have shown, in one study, to have fairly remarkable protective effects on the pancreas and preserve insulin secretion
One study noted that a saponin in Gynostemma Pentaphyllum is able to selectively activate LXRα, an enzyme highly localized to the liver that plays a role in cholesterol regulation.[75]
A study incubating hepatocytes with a high glucose and linoleic acid content (to mimic the conditions which damage liver cells during NAFLD[76][77]) found that an ethanolic extract of Gynostemma pentaphyllum was able to attenuate the concentration of triglycerides and cholesterol in hepatocytes in a concentration dependent manner between 100-300mcg/mL.[78] A reduction of F2-IsoPs was noted (although unreliable) and thought to be related to anti-oxidant properties; an increase of nitrate concentration was noted when coincubated with fatty acids only.[78]
Hepatic Stellate cell growth has been shown to be inhibited in vitro at 500μg/mL by Gypenosides via inhibiting the Akt/p70s6k pathway[79] and suppressing the secretions of the cytokines MCP-1 (40%), VEGF (17%), and TIMP-1 (25%) relative to untreated control;[80] this inhibition of MCP-1 also occurs with suppressed mRNA content, which is independent of the Akt/p70s6k pathway.[80] A reduction in type I procollagen also occured in a dose-dependent manner, although on all markers concentrations of 100-400mcg/mL were much less effective than 500mcg/mL.[80] These mechanisms may underlie the anti-fibrotic effect observed in vivo, when rats given Gynostemma Pentaphyllum experienced less collagen growth in their livers in response to a fibrosis-inducing toxin (CCl4).[81]
General protective effects from mixed anti-oxidant and anti-inflammatory mechanisms, may be anti-fibrotic and protect liver cells during instances of NAFLD
In rats given a high fat and cholesterol diet with some alcohol (to induce hepatic steatotosis) Gypenosides given at 15, 30, or 60mg/kg noted that the high dose group was approximately as effective as Silymarin at 23mg/kg in attenuating weight gain over 10 weeks and attenuating the hepatic index, but was more effective at reducing intrahepatic triglycerides (although PPARα mRNA levels were similar between groups; both higher than control).[82] ALT and AST were reduced similarly in the 30-60mg/kg Gypenoside groups as was the Silymarin group.[82]
One pilot study that compared 80mL Gynostemma Pentaphyllumtea against placebo in persons with Non-Alcoholic Fatty Liver (NAFLD) in conjunction with dieting noted that while diet was effective at all time points, the addition of tea failed to exert any significant benefit at 2 months but at 6 months was associated with significantly improved insulin sensitivity, weight loss, and serum liver enzyme profile relative to dieting placebo.[83]
In instances of high liver fat (NAFLD), Gynostemma Pentaphyllum has shown benefit following oral administration; only one human study using low dose tea but showed benefit over 6 months
Gypenosides may have protective effects against renal fibrosis via attenuating changes in TGF-ß1, CTGF, and Smad7 (proteins involved in pathogenesis of fibrosis)[84] and a single dose of 200mg/kg oral Gypenosides has shown to reverse the increase in urinary protein excretion induced by 10mg/kg Indomethacin, trending (nonsignificantly) to be less than control rats.[85] An increase in urinary N-acetyl-β-glucosaminidase was noted with the paired group (usually indicative of tubular toxicity), but there was no group taking Gypenosides in isolation to assess whether this is a per se effect of Gypenosides.[85]
Protective effects against fibrosis may also apply to the kidney, and although one study noted a normalization of urinary protein (indicative of renal protection) some biomarkers were not ideal; further research is needed
When 200mg/kg Gypenosides is taken 30 minutes prior to an overdose of NSAIDs (10mg/kg Indomethacin), the Gypenosides exert good protection of NSAID-induced ulcer inductions as assessed by ulceration area (mm3); reducing the ulcer by approximately 91%.[85] Similar protective effects are observed in the intestines where ulceration was reduced by 88% and increases in haptoglobin (serum) and haemoglobin (caecal) with Indomethacin were effectively normalized.[85] Protection against Helibactor Pylori induced ulcers,[86]stress-induced ulcers, and acid with alcohol induced ulcers.[87]
Appears to be quite an anti-ulcer agent in repeated animal studies against a variety of ulcer inducing agents
In a study on Indomethacin-induced toxicity, it was found that while intervention with Indomethacin did not alter intestinal microflora that Gypenosides at 200mg/kg (with Indomethacin, no Gypenoside-only group) was associated with a decrease in lactose-fermenting bacteria from 88-89.7% of bacteria to 25%; this was accompanied by an increase in bacteria per gram of tissue by 7.3-fold (Indomethacin) and 18-fold (Gynostemma and Indomethacin).[85]
May interaction with gut microflora, practical significance unknown and the study not adequately designed to assess the impact of Gynostemma Pentaphyllum per se
One study in Guinea pigs noted that while injections of 2.5-10mg/kg Gypenosides (or alternatively, 0.7mg/kg Gypenoside III and 0.3mg/kg Gypenoside VIII) caused a slight decrease in pulmonary ventilation pressure and resistance at the highest dose, all doses were effective in reducing histamine-induced constriction to a degree (66-68% inhibition with Gypenosides, no dose dependence noted).[88] In response to an antigen (which induces bronchoconstriction), 10mg/kg Gypenosides caused 80% inhibition of constriction which was similar to the active control of 10mg/kg Sodium Cromoglicate.[88]
May have anti-histamine mechanisms and preserve an 'open airway' through inhibiting constriction, without per se causing dilation
An extract of Gypenosides at 60-180ug/mL in SAS oral cancer cells is able to increase cell count in the G0/G1 and subGo/G1 phases and decreased S phase count; this was secondary to a calcium and ROS-dependent induction of apoptosis in a time and concentration dependent manner with 180ug/mL for 72 hours causing near absolute apoptosis via mitochondrial caspase release[89][90] and possibly by inhibiting DNA repair in SAS cells.[91] Cytochrome C and Endo-G have been noted to be released from the mitochondria (indicative of disturbed membrane potential) and GADD153 induction and nuclear translocation has been noted to be dependent on catalase (and thought to be related to ER stress).[92]
Gypenosides may also have anti-proliferative effects in this same cell line (SAS) as 90-180mcg/mL Gypenosides for 24-48h in vitro noted that while 90mcg/mL greatly attenuated migration, 180mcg/mL at both time points abolished migration.[90] Using a Matrigel assay, 90mcg/mL reduced migration (32-46%) and invasion (28-65%) while 180mcg/mL further reduced migration (63-78%) and invasion (51-80%) in a time dependent manner.[90] This was thought the be related to suppression of MMP proteins (2, 7, 9) and NF-kB.[90][93]
In mice injected with SAS cells to induce a tumor, injections of 20mg/kg Gypenosides for 28 days decreased tumor weight by 34% while the active control group (2mg/kg Doxorubicin) halved tumor size.[89]
Appears to have repeated in vitro evidence, and one mouse study suggesting it can be useful to reduce the size of oral cancer cell tumors; it underperformed relative to the reference drug Doxorubicin
In a HL-60 myeloid leukemia cells, gypenosides were shown to induce time and concentration dependent reductions in cell viability with 200ug/mL reducing survival to less than 20%. These changes were associated with an increase in G0/G1 cell count and a decrease in S phase, thought to be through a decrease in mitochondrial permeability and an increase in caspase release associated with an increase in intracellular calcium and ROS.[94] Another test in WEHI-3 (myelomonocytic leukemia macrophage-like) leukemia cells also noted DNA damage induced by Gypenosides reaching sub 40% viability after 48 hours of 200ug/mL and sub 20% after 72 hours of 150ug/mL, associated with the same cell phase changes and pro-oxidative mitochondrial pathway.[95]
In mice given injections of HL-60 (to induce tumor formation) given either 5 or 20mg/kg injections of Gypenosides every third day for a period of 4 weeks tumor size was reduced 56% with the higher dose with 5mg/kg not being significantly different than control.[94] Another study with daily injections of 2-4mg/kg total Gypenosides after injection with WEHI-3 leukemia cells noted dose-dependent prolongation of survival time (from 40% to 70% over 2 weeks),increases in megakaryocytes and CD3/CD19 cells, and a decrease in spleen weight.[95]
Possible anti-leukemic effects which have been noted twice in mice injected with leukemic cells; no comparison to a reference drug to assess potency, however
A screening study in Hep3B cells to assess bioactives that can induce apoptosis or halt proliferation of this cell line noted that the saponin fragment could reduce proliferation to 22.4% at 100ug/mL and the flavonoid fragment to 14.6% at 100ug/mL (IC50 47.6ug/mL and 57.8ug/mL respectively).[13] In Huh-7 cells, Gypenosides appear to induce apoptosis by a ROS and Calcium-mediated increase in mitochondrial membrane permeability which induces caspase release[96] and similar apoptotic results to these two cell lines (Hep3B and Huh7) have been seen in HA22T cells.[97][98]
Appears to induce cell death in a variety of liver cancer cells, no in vivo evidence
In a preliminary study A549 lung cancer cells, the molecule gypensapogenin C appears to induce cytotoxicity at an IC50 of 0.11+/-0.3μM.[2] In general, mixed Gypenosides can induce concentration and time dependent apoptosis in A549 cells associated with cell accumulation in G0/G1 and sub-G1 phases and DNA fragmentation and caspase release.[99]
General cell killing effect in lung cells; practical significance unknown
Gypensapogenin C appears to induce cytotoxicity in U87 glioblastoma cells with an IC50 of 0.58 ± 0.16μM.[2]
A study assessing C6 glioma tumor cells, 24-240mcg/mL (ethanolic extract) acutely reduced H2O2 levels in a concentration dependent manner with an induction of SOD up to 2-fold over 48 hours of incubation at 120mcg/mL or above;[100] this surprisingly occurred with a concentration and time dependent decrease in cell viability in tumor cells associated with caspase-3 release (almost abolishing proliferation at 72 hours with 240mcg/mL) and did not seem to influence non-cancerous astrocytes within the tested dose range.[100]
Standard cell killing effects in glioma cells, with at least one study noting that healthy cells were not affect at this concentration; no living models have been tested yet
Using a saponin-rich fraction of Gynostemma pentaphyllum, a weak inhibition of proliferation (12.1%) was noted with 10ug/mL increasing to over 80% at 100ug/mL with slightly more effective inhibition at graded concentration of a flavonoid rich extract up to 150ug/mL; the IC50 values were 33.3μg/mL and 39.3μg/mL respectively.[29] These effects were accompanied by an increase in sub-G0/G1 and decrease in G0/G1 phase and related to the mitochondrial-caspase pathway.[29]
Possible anti-prostate cancer effects, practical significance unknown and not overly potent either
Gypenosides appears to reduce NAT1 protein and mRNA content in a dose-dependent manner, which has been associated with less DNA adduct formation in HeLa cells incubated with 2-aminofluorene (which binds to DNA after being acetylated by NAT1 enzymes).[101][102]
Practical significance of oral supplementation unknown
Gypenosides are able to cause apoptosis in Colo205 cells in a concentration and time dependent manner with an IC50 of 113.5ug/mL, which is related to mitochondrial caspase release from ROS and calcium; an increaes in G0/G1 and subG1 phases are seen in this cell line.[103] This study also noted increase levels of p15, p16, p21, p27, and p53, and the authors hypothesized the mechanism of action was related to inducing p53 (which would positively influence p21 and p27, and the increase in Bax would mediate apoptosis).[103]
Possible anti-cancer effects, with moderate to weak potency (judging by the IC50 values) and no living system tested
SK0506 is a herbal mixture of Coptis Chinensis (source of Berberine), Salvia miltiorrhiza, and Gynostemma Pentaphyllum; used for the treatment of diabetes. A rat study using 1000mg Gypenosides, 800mg Berberine, and 500mg Tanshinone IIA per kg bodyweight in rats with metabolic syndrome for 4 weeks noted that rats fed SK0506 was able to reduce plasma triglycerides (34%), NEFA (22%), and cholesterol (31%) with some ability to reduce insulin (37%); in comparison to the active control of 3mg/kg Rosiglitazone, SK0506 outperformed on lipid parameters and underperformed for reducing insulin and improving insulin sensitivity while both failed at reducing glucose significantly over 4 weeks. When measuring body weight, the SK0506 group experienced a decrease in fat mass and body weight while the active control Rosiglitazone expectedly increased body weight.[104]
Possible synergism among these compounds for the purpose of being anti-diabetic, although delineation between the active components has not been done yet
Grape Seed Extract (GSE; essentially a source of Procyanidin compounds) has been tested alongside Gypenosides at 40mg/kg each supplement (against other groups of 80mg/kg GSE, 80mg/kg Gypenosides, and 500mg/kg Metformin as active controls) in mice on a high fat paired with fructose diet that suffered from hepatic insulin resistance (due to diet composition) over a period of 6 weeks.[105]
This study noted that the combination therapy group outperformed both isolated Gypenosides and isolated GSE in reducing the percent body fat gained slightly which was not significantly different than control and normalized serum glucose, insulin, and insulin sensitivity; combination therapy was equally effective as Metformin at reducing serum insulin while being slightly (but significantly) more effective at reducing serum glucose and improving insulin sensitivity.[105] Combination therapy, but not either treatment in isolation, was equally effective as Metformin in response to an oral glucose tolerance test.[105]
One study in rats suggest that Grape Seed Extract and Gypenosides are highly synergistic in improving central insulin resistance, and combination therapy rivalling the efficacy of Metformin
Oral doses up to 750mg/kg of Gynostemma Pentaphyllum water extract failed to exert any appreciable toxic effects in rats over a period of 6 months aside from a slight but nonsignificant reduction in weight, seen in a dose-dependent manner.[106] No differences were observed in food intake or behaviour, organ weight, or hematological parameters.[106] A rough estimate for the equivalent human dose of 750mg/kg in rats is 120mg/kg water extract in humans,[107] or 8g daily for a 150lb person. Oral doses of up to 400mg Gynostemma Pentaphyllum for 2 months has been shown to be safe in otherwise healthy humans.[1]
No toxicity has been reported with moderate to high usage of Gynostemma, although evidence is limited
A hot water extract of Gynostemma Pentaphyllum failed to exert mutagenicity (induce mutations) to Salmonella typhimurium, TA 98, and TA 100 with or without metabolic activity.[108] When testing coincubation with known carcinogens, Gynostemma hot water extract protected against 7 including Benzo(a)pyrine induced mutagenesis (a carcinogen found in cooked meat) although it augmented mutagenicity from the two test compounds 2-AA (TA98 strain) and MNNG (TA100 strain) with decreasing augmentation as the concentration increased.[108]
Gynostemma has been reported to induce DT-diaphorase activity in murine hepatoma cells in a concentration dependent manner,[108] which is a mechanism associated with protection from carcinogens.[109]
Mixed effects on genomic damage, although for the most part it appears to protect the genome from damage
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- ^ a b Sun H, Zheng Q. Haemolytic activities and adjuvant effect of Gynostemma pentaphyllum saponins on the immune responses to ovalbumin in mice. Phytother Res. (2005)
- ^ a b Yuan H, et al. Gynostemma pentaphyllum protects mouse male germ cells against apoptosis caused by zearalenone via Bax and Bcl-2 regulation. Toxicol Mech Methods. (2010)
- ^ Huang TH, et al. A novel LXR-alpha activator identified from the natural product Gynostemma pentaphyllum. Biochem Pharmacol. (2005)
- ^ Feldstein AE, et al. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology. (2004)
- ^ Malhi H, et al. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem. (2006)
- ^ a b Müller C, et al. Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract. Phytomedicine. (2012)
- ^ Chen MH, et al. The molecular mechanism of gypenosides-induced G1 growth arrest of rat hepatic stellate cells. J Ethnopharmacol. (2008)
- ^ a b c Chen MH, et al. The inhibitory effect of Gynostemma pentaphyllum on MCP-1 and type I procollagen expression in rat hepatic stellate cells. J Ethnopharmacol. (2009)
- ^ Chen JC, et al. Therapeutic effect of gypenoside on chronic liver injury and fibrosis induced by CCl4 in rats. Am J Chin Med. (2000)
- ^ a b Qin R, et al. Protective effects of gypenosides against fatty liver disease induced by high fat and cholesterol diet and alcohol in rats. Arch Pharm Res. (2012)
- ^ Chou SC, et al. The add-on effects of Gynostemma pentaphyllum on nonalcoholic fatty liver disease. Altern Ther Health Med. (2006)
- ^ Zhang Y, et al. Gypenosides inhibit renal fibrosis by regulating expression of related genes in rats with unilateral ureteral obstruction. J Nephrol. (2011)
- ^ a b c d e Hesse C, et al. Phytopreventative effects of Gynostemma pentaphyllum against acute Indomethacin-induced gastrointestinal and renal toxicity in rats. Phytother Res. (2007)
- ^ Therapeutic role and its mechanism of gypenosides on delayed healing of experimental gastric ulcer induced by NCTC11637 strain HP in rats.
- ^ Rujjanawate C, Kanjanapothi D, Amornlerdpison D. The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino. Phytomedicine. (2004)
- ^ a b Circosta C, et al. Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs. J Pharm Pharmacol. (2005)
- ^ a b Lu KW, et al. Gypenosides suppress growth of human oral cancer SAS cells in vitro and in a murine xenograft model: the role of apoptosis mediated by caspase-dependent and caspase-independent pathways. Integr Cancer Ther. (2012)
- ^ a b c d Lu KW, et al. Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2 -9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways. Hum Exp Toxicol. (2011)
- ^ Lu KW, et al. Gypenosides causes DNA damage and inhibits expression of DNA repair genes of human oral cancer SAS cells. In Vivo. (2010)
- ^ Chen JC, et al. Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells. Oral Oncol. (2009)
- ^ Lu KW, et al. Gypenosides inhibited invasion and migration of human tongue cancer SCC4 cells through down-regulation of NFkappaB and matrix metalloproteinase-9. Anticancer Res. (2008)
- ^ a b Lin JJ, et al. Molecular evidence of anti-leukemia activity of gypenosides on human myeloid leukemia HL-60 cells in vitro and in vivo using a HL-60 cells murine xenograft model. Phytomedicine. (2011)
- ^ a b Hsu HY, et al. An experimental study on the antileukemia effects of gypenosides in vitro and in vivo. Integr Cancer Ther. (2011)
- ^ Wang QF, et al. Gypenosides induce apoptosis in human hepatoma Huh-7 cells through a calcium/reactive oxygen species-dependent mitochondrial pathway. Planta Med. (2007)
- ^ Wang QF, et al. Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides-induced apoptosis in human hepatoma cells. Cancer Lett. (2002)
- ^ Chen JC, Chung JG, Chen LD. Gypenoside induces apoptosis in human Hep3B and HA22T tumour cells. Cytobios. (1999)
- ^ Lu HF, et al. Gypenosides induced G0/G1 arrest via inhibition of cyclin E and induction of apoptosis via activation of caspases-3 and -9 in human lung cancer A-549 cells. In Vivo. (2008)
- ^ a b Schild L, et al. Selective induction of apoptosis in glioma tumour cells by a Gynostemma pentaphyllum extract. Phytomedicine. (2010)
- ^ Chiu TH, et al. Gypenosides inhibited N-acetylation of 2-aminofluorene, N-acetyltransferase gene expression and DNA adduct formation in human cervix epithelioid carcinoma cells (HeLa). Res Commun Mol Pathol Pharmacol. (2004)
- ^ Chiu TH, Chen JC, Chung JG. N-acetyltransferase is involved in gypenosides-induced N-acetylation of 2-aminofluorene and DNA adduct formation in human cervix epidermoid carcinoma cells (Ca Ski). In Vivo. (2003)
- ^ a b Chen JC, et al. Gypenosides induced apoptosis in human colon cancer cells through the mitochondria-dependent pathways and activation of caspase-3. Anticancer Res. (2006)
- ^ Tan Y, et al. Chinese herbal extracts (SK0506) as a potential candidate for the therapy of the metabolic syndrome. Clin Sci (Lond). (2011)
- ^ a b c Zhang HJ, et al. A combination of grape seed-derived procyanidins and gypenosides alleviates insulin resistance in mice and HepG2 cells. J Food Sci. (2009)
- ^ a b Attawish A, et al. Chronic toxicity of Gynostemma pentaphyllum. Fitoterapia. (2004)
- ^ Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers.
- ^ a b c Kulwat C, et al. Antimutagenicity and DT-diaphorase inducing activity of Gynostemma pentaphyllum Makino extract. J Med Invest. (2005)
- ^ Talalay P. Mechanisms of induction of enzymes that protect against chemical carcinogenesis. Adv Enzyme Regul. (1989)


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Having a bedroom without enough space, means you have to look for hanging bed ideas. This is essential if the rooms are designed as mere sleeping areas. Here are some ideas that help in maximizing space and allow the space to be used perfectly.
Bunk beds
Bunk beds are the best hanging bed ideas that are space saving solutions as well. These are for children sharing a room. Bunk beds are good option for toys storage and for guest bedrooms. These also function as economy canopy bed with curtain rods as addition. Ideal for children, but avoid the top bunk for children less than 6 years.
Mezzanine/Loft beds
These are same as bunk beds, but lack an arrangement for second sleeping on the bottom. Some beds feature elaborate setups and such beds include steps, shelves and matching furniture. While other beds come featuring a bed and a ladder. These loft beds are ideal for smaller rooms and college dorm rooms.
Murphy beds
This bed type flips against a wall, if it is unused. It allows more floor space and the Murphy beds are loved by kids. They have comfortable mattresses and are easy to use. They can be used as a desk when the bed is away.
Hanging beds
These beds hang from the ceiling and do not give enough storage space. This is one of the hanging bed ideas that now come with a pulley system such that the bed is swung to the ceiling. The ceiling needs to be fairly high for this bed to be hung and care must be ensured so that the pulley handles the weight of the bed and the occupant.
Bed up
This refers to a French concoction where the bed is on tracks and there are fold-down legs that can be raised and lowered same as any hanging bed on pulleys, but for the fact that it is anchored to the wall. Thus it offers solid support from the legs and is less movable.

subset: commoncrawl


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June 28, 2019 | #4852
Season 48 Episode 4852 | 27m 46s
The panel discusses the governor's struggle with the GOP legislature over an unfinished budget. The guest is State Supreme Court Chief Justice, Bridget McCormack. Kyle Melinn, Cheyna Roth and Bill Ballenger join senior capitol correspondent Tim Skubick.
Aired: 06/28/19Video has closed captioning.


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Obviously some minor verbage that we need to go along with this fabulous offer: Only one session per client. To be used for session fee only, and does not include any prints or products. Sale good from November 30, 2010 to December 5th 2010. Can be applied to any of our portrait sessions; maternity, newborn, children, HS seniors, and family. (Family sessions for 5 people or less) Only valid within 40 miles of Plainfield, IL. But don't worry, this covers A LOT of ground! Good for 2011 sessions only. Can not be combined with any other offer.
If you're interested, press the link HERE and it will get you to where you need to be! Happy Holidays!


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How immune cell 'anti-heroes' are kept in lockdown until needed
Our immune system balances on a knife edge, ready to attack foreign invaders but ignoring our own cells and organs. New research shows a class of antibody called IgD plays a role policing rogue immune cells. Simon Teteris reports.
In the Hollywood blockbuster Suicide Squad, supervillains are kept locked away until they're needed to stop an army of evil invaders, becoming anti-heroes that save the day.
Something similar happens in our body every day, except the supervillains are self-reactive antibody-producing immune cells that, when re-educated and let loose, attack the new invaders threatening our health.
Zahra Sabouri and Samuel Perotti from Australian National University and colleagues from Australia and Turkey discovered how these potentially dangerous self-reacting cells are placed on "lockdown" – kept alive but unresponsive until they recognise a foreign pathogen and kick-start a protective immune response.
As these self-reacting immune cells are also seen in blood cancers such as leukaemia and lymphoma, this discovery may help to further understand how these cancers arise.
The work was published in Nature Communications.
Currently, more than five million people worldwide suffer from the autoimmune disorder lupus, where the immune system mistakenly attacks normal, healthy tissues such as small blood vessels in the kidneys, producing inflammation, pain and organ failure.
But our immune system must have developed ways to deal with cells that produce these self-reactive antibodies – otherwise, the number of people suffering autoimmune diseases would be much higher.
The new study shows how a type of antibody called immunoglobulin D (IgD), which hangs off the surface of antibody-producing immune cells called B cells, manages this.
Using mice, Sabouri, Perotti and their crew examined genes activated in locked down B cells, with and without IgD on their surface.
They found 220 genes were specifically activated in these cells, with IgD controlling around a third – boosting expression of some but dialling down others.
Intriguingly, IgD on the surface of self-reacting B cells helped them survive and multiply when locked away in immune tissues called germinal centres.
"We think that the large-scale lockdown of B cells is the immune system's way of avoiding 'holes' in its defensive line, so that it is ready to respond to any conceivable invasion," study co-author Christopher Goodnow, also at Australian National University, says.
"If every B cell capable of producing autoantibodies was removed, rather than kept in lockdown, we would severely limit the number of foreign invaders that our immune system could recognise.
"By locking down B cells, and keeping them alive, IgD strikes a delicate balance between protection from invaders and avoiding an immune attack on the body's own tissues."
- http://www.nature.com/ncomms/


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Partnerships with industrial heritage museums and local libraries are integral to this project. Our current partners include:
The National Railway Museum, York
National Mining Museum Scotland
National Coal-Mining Museum for England
Historic Environment Scotland: Stanley Mills
Verdant Works, Dundee Heritage Trust
Quarry Bank Mill, National Trust
New Lanark World Heritage Site
Working-Class Movement Library, Manchester
The Mitchell Library, Glasgow Life
Bradford and Keighley Libraries: Local Studies
Dundee Central Library: Local History
The Armstrong Browning Library and Museum, Baylor University, Texas
We are also delighted to be working with playwright Martin Travers and Guy Hollands Associate Director (Citizens Learning) from the Citizens Theatre, Glasgow, and with musicians Findlay Napier, Gillian Frame and Jennifer Reid.
'Piston, Pen & Press' welcomes interest from new heritage and creative partners and we would be happy to involve you in our events. Please email a member of the project team for more information.


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Ansel Elgort Will Lead Steven Spielberg's 'West Side Story' Remake
All that Stagedoor Manor experience is going to serve Ansel Elgort well in his next role. The Baby Driver star has landed the lead role in Steven Spielberg's West Side Story, a remake of the Stephen Sondheim Broadway musical.
West Side Story will have a script by Tony Kushner, adapting the classic New York City story of the love between Tony, former member of the Jets street gang, and Maria, younger sister to the leader of a rival gang. After a few years in which Spielberg tried to fit West Side Story into his crammed schedule he finally began a casting search earlier this year. Elgort makes for a natural fit with his song and dance abilities, and I think he's still a fresh enough face that he comes across like an unknown to most people. Of course, that could be a double-edged sword if Elgort doesn't have the charisma to pull off such an iconic role. No word on who will play Maria, but I'm guessing Spielberg goes for a big name.
Production on West Side Story begins next summer, after Spielberg wraps up Indiana Jones 5. Elgort will be seen next in the sci-fi drama Jonathan. [Variety]


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Find Top-Rated Warm Springs Lighting Companies
There are 6 top-rated lighting companies in your area.
Arcbazar Inc
Business Description: ARCBAZAR provides online architectural design. Services include: New Residential, Remodeling, Interior Design, Landscape, and Commercial Spaces. Clients launch a competition for a project online at ARCBAZAR.com by providing a brief description and images/dimensions. Several Architects & Designers participate in the competition. By the end, Clients receive multiple design packages and choose the best solution. To view completed projects, please visit www.arcbazar.com
Risher's Cleaning & Handymen
Business Description: We are your one stop shop for all painting, house cleaning and handyman services! Additional BBB: www.bbb.org/arkansas/business-reviews/cleaning-services/squeaky-kleen-in-wesley-ar-90330085. Lic #034895129
Affordable Fans - The Fan Doctor
Business Description: Owner operated. Additional DBA: The Fan Doctor. Licensed electrician in New Hampshire & Massachusetts. Over 30 years experience.
Alexander Technical Resources
Business Description: Free Phone Consultation. Not sure if we can help? Give us a call, it's on us! We are more than happy to talk with you and discuss your computer problems. Fast service. In some cases we can help you right now! If not, we will schedule an appointment that fits your schedule. If you receive our answering service, please leave us a message. We will call you back as soon as possible. Domestic Based Support. Our company is based right here in the United States and all of our technicians speak clear, fluent English. Safe Interaction. By using our online support center, no one has to come out to your home to fix your computer. That means no strangers in your home and you don't even have to get dressed, if you don't want to. Extremely Affordable & Convenient. Unhooking your computer, dragging it out to the car, then driving to the store and dragging in there and waiting for weeks to get it back and then pay hundreds of dollars for such fantastic service. That's the typical experience for most users. Most Issues are software based. In our experience. 85% of user's problems are either software or operating system problems due to bugs, worms, virus', Trojans, malware, grayware or spyware related. As long as your computer turns on and has an internet connection, we can probably solve your issue. If we find that your issue is a hardware issue, we will recommend a trusted, local support company to help you further, if possible.
Staley Electric
Business Description: *We Have a Proud 50 Year History of Serving Our Customers with World Class Support of Their Detroit Diesel and Allison Equipped Products. *It is Our Goal to Maintain a Leadership Role in the Application of Leading Edge Technology in Transportation, Energy, Agriculture and Power Generation. In Conjunction with Our Business Partners, We Offer Products and Services that have a Long Record of Reliability while Providing the Most Recent Advancements in Technology to Meet Our Customer's Needs. *Your Input is Very Important to Us so if You Have any Questions or Comments, We Would Invite You to Use Our E-mail Links. We Look Forward to Providing You with a Service Experience that Demonstrates Why United Engines has Earned the Highest Customer Satisfaction Rating in the Detroit Diesel Distribution Network.
Classic Copper Works
Business Description: Classic Copper Works uses time honored German copper smith techniques handed down from father to son and passed on to our highly skilled artisans. We specialize in the fabrication of custom copper & bronze products and other metal specialties. WE DO NOT OFFER REPAIR SERVICES OF ANY KIND. Additional phone number - (888) 908-5339.
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USA Alarm Service, Inc
Business Description: USA Alarm is a national company that has more than two decades of experience and an award winning command center that protects more than 700,000 homes and businesses through the United States, 24 hours a day and 7 days a week. We have offices located throughout the US, with two main offices in Indianapolis, Indiana and Post Falls, Idaho.
Rating Not Available
Pros who have not received a review in the last three years do not have a rating displayed.3Reviews
Amp 1 Electric Service LLC
Business Description:
Rating Not Available
Pros who have not received a review in the last three years do not have a rating displayed.1Review
Another Level Cleaning Services
Business Description: Exterior Cleaning/Restoration Artist. "We Make Beautiful Happen"
Rating Not Available
Pros who have not received a review in the last three years do not have a rating displayed.1Review
Austin Electric, LLC
Business Description: We are a service company prepared to handle all of your electrical and lighting needs. We believe our customers should be treated like family, and we will do our level best to earn your repeat business.


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There are many different types and grades of doctors you may meet during your cancer care experience.
Most doctors who treat cancer are based in hospitals, but general practitioners (GP's) are also involved in diagnosing and caring for cancer patients. The GP (general practitioner or family doctor) is the doctor who is responsible for your medical care at home. He or she is usually the first doctor you will see he/she will refer you for tests and investigations, or refer you to a hospital for treatment.
Your GP can coordinate the help you need and arrange help from other healthcare professionals, such as community nurses. He or she will continue to provide general medical care for you that is not related to your cancer. They will receive information regarding your hospital consultations, and if/when you have been an inpatient.
Among hospital doctors, the most senior specialists are consultants who supervise the work of a team of doctors. The team may include a specialist registrar (a senior doctor in specialist training) and associate specialists or staff grade doctors.
Other doctors in the consultant's team might include what was formerly known as house officers and senior house officers. They are sometimes called foundation year or junior doctors but are fully qualified members of the team. F1 doctors are in their first year of post graduation medical degree, after which they achieve full registration with the General Medical Council (GMC). By the end of year two, (F2) they will have chosen the area of medicine they wish to specialise in.
Medical students are training to become doctors and learn by being involved in treating and caring for patients. However you can say if you do not want a medical student to be present, or if you want to talk privately to your doctor. You have a right to privacy and this will not affect your care.
There are many different kinds of doctor or surgeon involved in diagnosing, treating or caring for cancer patients. The kind of doctor or surgeon will depend on your type of cancer and other needs you may have. You can find out more about hospital doctors at types of hospital doctors explained.


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Canoes listed as 'In Stock' are available at our UK warehouse and will be delivered to your selected Test Centre normally within 1-3 weeks of Order Confirmation.
If the canoe you wish to purchase is listed as a 'Special Order' item, please be aware that these are produced to order in Canada and will normally be delivered to your selected Test Centre up to 12 weeks after the closing date for orders on that particular container. A countdown to each container closing date is displayed below. Please note, from time to time we may close orders early as and when the current container is filled. If there's one thing we can say with confidence though, it's that an Esquif canoe is worth waiting for!
As soon as your order has arrived with your chosen EsquifUK Test Centre and is ready for collection, your test centre will notify you by email; when collecting your canoe(s), it is important that you check for any damage which may have occurred during transit, as neither EsquifUK, nor our Test Centres are able to accept responsibility for any such damage notified after collection.


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If you need urgent assistance where you are experiencing domestic and family violence you should contact DV Connect at http://www.dvconnect.org/ or 1800 811 811 (24hours/7days). Counselling and assistance are also available at the Working Against Violence Support Services (WAVSS) at Logan and in the Redlands and other local services. You can contact WAVSS at http://www.wavss.org or (07) 3808 5566 (Logan) and (07) 3286 7766 (Redlands).
What is "domestic violence"?
Domestic violence has a broad definition and can range from physical or sexual assault to verbal, emotional and psychological abuse. Domestic violence can also take on other forms such as 'financial abuse' where one person limits access to assets or money, usually as a way of controlling the other person. Threats, coercions and other methods of control are also recognised forms of domestic violence.
What types of relationships are covered?
A domestic violence order can only be made where there is a domestic or family relationship between the parties. Examples include:
Who can apply for a Domestic Violence Protection Order?
If you have experienced domestic violence then you can report this to Police and they may make the application for an order on your behalf. Alternatively, you can make an application yourself, without the assistance of police. You can also authorise someone to make an application on your behalf, such as a family member or friend, however, this person must be over 18 years of age.
How do I make an application for a Domestic Violence Order?
There is a specific application form to fill out. You will be referred to as the 'Aggrieved' or the 'Applicant'. The other party will be referred to as the 'Respondent'. If you are making the application yourself, you or your lawyer should complete the form and file it at your nearest Magistrates court. You can ask the court to put certain 'conditions' on the Order, if one is made, such as that the Respondent cannot come to your house, or place of work, or cannot contact you. When your application is filed, the court will give you a date that you (and your lawyer, if you have one) will have to appear to have the application considered in the first instance. Usually that day or within the next couple of days, and this is usually done 'ex parte', which is a legal term meaning 'without the other party there'.
What happens at the first court date?
The court is always 'closed' when matters concerning Domestic Violence Orders are heard. This means that only the parties and their legal representatives are allowed inside the courtroom. If you do not have a lawyer the court may allow you to have a support person. The Magistrate will consider your application. If the Magistrate considers it necessary, he or she will make a 'Temporary Protection Order' (TPO) that will state certain conditions depending on the circumstances. For example, the TPO may require that the Respondent be of good behaviour towards the Aggrieved and not commit acts of domestic violence, or that they remain a certain distance from the Aggrieved, and where the Aggrieved lives, works or frequents. It is then the job of the police to serve your application, and the TPO (if one is made) on the Respondent. The TPO is not in effect until it is served on the Respondent. A second court date will be set.
What happens after the Respondent is served with my application?
The Respondent may be at the court this time and will be asked if he or she consents to the Domestic Violence Order being made. Sometimes the Respondent will agree to the Order being made 'without admissions' which means that they do not admit that there have been any acts of domestic violence, but they consent to the Order in any event. If the Respondent does not attend the court will consider making the Order final provided the Respondent has been served. Alternately, the Respondent may agree to the Order but only if certain conditions are removed. If the Applicant does not want those conditions removed, then the matter will be set down for a hearing. Otherwise, if the Respondent does not agree to consent to the Order in any terms, then the matter is set down for a hearing.
If the Order is consented to
If the Respondent consents to the Order being made, then the Magistrate will make that Order, usually to remain in place for two years, unless otherwise agreed by the parties.
If the Order is not consented to
If the Respondent does not consent to the Oder being made, or does not agree to the conditions of the Order, then the matter is set down for a hearing. If there is a TPO in place, the Magistrate will usually extend that order until the matter goes to that hearing. If there is no TPO, the Magistrate can make one, or decide not to make one and wait until the matter is decided on a final basis at the hearing. The Magistrate will make a 'Directions Order' that sets out certain dates. The first date will be a date by which the Applicant must file his or her own affidavit, and affidavits of any other witnesses who will give evidence at the hearing. An affidavit is a sworn written statement that is filed in court and used in court proceedings, such as hearings.
What happens at the hearing?
A hearing is where the parties bring the matter before the Magistrate and present their application and defence, and support their positions with evidence such as affidavit material and witnesses. The Magistrate will consider all of the relevant evidence and make a decision in accordance with the Domestic and Family Violence Protection Act 2012 (Qld). The Magistrate will then decide whether or not to make an Order and what conditions are to be imposed by any order made.
The Applicant will present their evidence and witnesses first. The Applicant and his or her witnesses will then be cross-examined by the Respondent. This is usually done by the Respondent's lawyer or barrister. If the Respondent does not have legal representation then they may do this cross examination themselves. Sometimes the Applicant may be understandably upset by this, especially where they have been the victim of severe abuse. In those circumstances, the Applicant may ask the court to make different arrangements for giving evidence under cross examination. You may want to consider asking your lawyer about this.
The Respondent will then present his or her defence and put forward a case that either there have been no acts of domestic violence, or that the order is not necessary or desirable.
Who can be a witness?
You can ask other people to provide evidence for you to help you at the hearing. If someone agrees to provide evidence, then that witness must make themselves available on the day of the hearing. If the witness provides an affidavit but does not make themselves available for cross examination on the day of the hearing then the court can decide how much weight, if any, it will give to the affidavit material.
What if the Respondent breaches a Temporary Protection Order (TPO)?
If there is a TPO in place, and the Respondent has been served with that order by police, then breaching the TPO is the same as breaching an Order that has been consented to or made by the court after a hearing.
What if the Respondent breaches the Domestic Violence Order?
'Breaching' the Order means that the Respondent has done something that is against the terms of the Order. For example, if the Order states that the Respondent cannot approach the Aggrieved within 100 metres, and then does so, this is a breach of the Order. The Aggrieved should then report this to the Police and the Police will investigate the incident.
If the Respondent commits an act of domestic violence that is, in and of itself a criminal act, for example a physical assault, he or she will be charged for the assault and for breaching the protection order.
If the Police are satisfied that an offence and/or a breach of the orders has occurred, then they will either arrest and charge the Respondent, or serve the Respondent with a 'Notice to Appear' in court to answer the charge or charges. These 'breach proceedings' are criminal in nature and therefore heard in an open court, except in limited circumstances.
If the Respondent pleads guilty to the offence and/or the breach of the order, he or she will then be sentenced. The punishment will depend on many factors, including the seriousness of the offence and the Respondent's criminal record. If the Respondent pleads "not guilty" to the charge or charges, the matter will go to a hearing.
What do I do if the Order is going to expire and I still want it in place?
You can apply to the court to have the Order extended. The court will extend an Order if you can show that it is necessary and desirable to do so.
Our circumstances have changed and I want to vary the Order
Sometimes parties can work things out and in those circumstances you might like to apply to the court to have the conditions of an order varied or withdrawn. If the order was made on a police application then this may be more difficult.
I am a Respondent to an application – What should I do?
It is likely that the first you will know about an application is when either the Applicant tells you, or when you are served with the application by the Police. The application and any temporary order will be explained to you. You will be advised of the next court date.
At the next court date you will have three options:
If you do not attend at court, the court will consider making the Order final provided you have been served.
You should seek legal advice about the effect that a protection order has on your personal circumstances before you consent to an order.