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A Review on the Phytochemical and Pharmacological Properties of Rosa laevigata : A Medicinal and Edible Plant

Rosa laevigata Michx., a medicinal and edible plant in China, has exerted a variety of medicinal values and health beneﬁts. This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of R. laevigata . According to these ﬁndings in the literature, ap proximately 123 chemical ingredients covering triterpenoids, ﬂavonoids, tannis, lignans and polysaccharides, have been characterized from various parts of this species. Among these isolates, 77 triterpenoids have been isolated and thus regarded as the primary and characteristic substance. Based on the chemical structures, most of the obtained triterpenoids can be classiﬁed into polyhydroxy triterpenoids and readily divided into four categories: ursane-type, oleanane-type, lupinane-type, as well as s eco -triterpenoids. The crude extracts and the puriﬁed compounds have demonstrated various pharmacological eﬀects in vitro and in vivo , such as antioxidant activity, immunomodulatory eﬀect, anti-inﬂammatory eﬀect, liver protection, kidney protection, cardiovascular protection, neuroprotective eﬀect and improvement of diabetic cataract. Noticeably, these pharmacological results of R. laevigata provide evidences for its traditional uses. In addition, these diﬀerent chemical ingredients existing in the title plant may have synergistic eﬀects. In conclusion, the chemical pro -ﬁles, including ingredients and structures, together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuﬀ and more attention should be paid to a better utilization of this plant.


Phytochemistry
Due to its significant pharmacological activities, the chemical constituents of R. laevigata have been extensively studied in the past decades. Up to date, approximately 123 ingredients covering triterpenoids, flavonoids, tannis, lignans and polysaccharides, have been isolated from different parts of this species. Among them, triterpenoids have been regarded as the principal and characteristic bioactive substances.
The first report of triterpenoids from R. laevigata can be traced back to 1991, when 11 chemical components including derivatives of ursolic (1-9, Table 1) and oleanolic acids (10-11, Table 1) were isolated from an acetone extract of the aerial parts of R. laevigata. 6) Among these compounds, 5 was assigned to be a new compound, with a hydroxyl group positioned at C-11 in the molecule. Noticeably, lots of ursane-type triterpenoids were isolated from R. laevigata, only compound 5 was found to possess hydroxyl group occurring at C-11. Since then, phytochemical researches on R. laevigata have been carried out scarcely. Till 2008, Yuan et al. reported the isolation of two new ursane-type triterpene glucosides featured with a heteroannular diene (12 and 13) from this species by bioassay-guided fractionation. 1) In the period 2010-2014, ongoing chemical investigations of R. laevigata afforded a variety of triterpenoids (15-52, Table 1) which were isolated for the first time from the title plant. [7][8][9][10][11] Apparently, these studies reinforce previous reports in indicating that triterpenoids are the predominant chemical constituents in R. laevigata. In particular, the occurrence of 28 in R. laevigata is more interesting, as it is reported for the first time in the family Rosaceae and may be useful as chemotaxonomic marker for the genus. 7) Additionally, bioassay-guided fraction led to the isolation of several novel triterpenoids, 8) for instance, 29 belongs to nortriterpenoid, possessing a conjugated diene between C-12 and C-17, 30 can be classified into triterpene lactone saponin, in whose structure, a six-membered lactone ring was formed between C-20 and C-28, while 31 and 32 are assigned to seco-ursane type triterpenes, bearing a 18,19-seco moiety in the molecules. Although triterpenoids with a p-coumaroyl group substituent were reported rarely, 38-41 were found to own a p-coumaroyl group substituent which was attached at OH-3 exactly. 9) Interestingly, 43 possessing aldehyde group moiety which occurs rarely in the natural plant, indicated that it might be artefact of the isolation procedure. 10) Moreover, another bioassay-guided isolation carried out by Yan et al. afforded a few of novel triterpenoids: laevigins A-D (44)(45)(46)(47). 11) Among them, 45 and 46 are newly described 18,19-secoursane-type triterpenoid saponins. This finding enriched the structure diversity of 18,19-seco-ursane-type triterpenoids and thus the chemical diversity of R. laevigata. In 2016, a novel skeleton natural product laevigaterpene A (53), featuring a rare 2-hemiacetal moiety in its A ring was found to exist in the title plant. 12) Additionally, laevigaterpene B (54), a new lupane-type triterpene belonging to aromatic ester triterpene derivative has been characterized in this study. 12) Besides, phytochemical investigation of roots of R. laevigata carried out by Dai et al. resulted in the isolation of a series of triterpenoids, especially, the following chemical components were obtained from this plant for the first time: 55-70. 13,14) More recently, a new triterpenic acid derivative was isolated from the roots of R. laevigata and elucidated as 71. In addition to 71, two known compounds 72 and 73 were obtained from the genus Rosa for the first time. 15) Separation of the MeOH extract of R. laevigata resulted in the characterization of a new 18,19-seco-ursane-type triterpenoid (74). 16) Gao et al. designed a method for the rapid and straight forward preparative scale purification of two polyhydroxy triterpenoids (14 and 22) from the fruits of R. laevigata. This method involves microwave-assisted extraction technology coupled with multi vacuum extraction columns. 17) R. laevigata var. leiocapus acts as a variety of R. laevigata, whose specific morphological characteristics of this species is attributed to its smooth fruits without any thorns. In 2019, as a part of our ongoing research on novel and bioactive triterpenes from Rosa genus, the fruit of R. laevigata var. leiocapus was subjected to a detailed phytochemical investigation, resulting in the isolation of three new nortriterpenes, designated as rosanortriterpenes A-C (75-77). To the best of our knowledge, this represented the first study on the chemical constituents of R. laevigata var. leiocapus. 18,19) In aggregation, 77 triterpenoids and the derivatives were isolated from R. laevigata till now, including 45 ursane-type triterpenoids, 13 oleanane-type triterpenoids, 8 lupinane-type triterpenoids, as well as 11 seco-triterpenoids. Generally, most of the triterpenoids obtained from R. laevigata can be classified into polyhydroxy triterpenoids, the main differences among them depended on the number of the hydroxyl groups and their substitution positions.
At present, there are many reports involved the flavonoids from R. laevigata, however, most of them are focused on the extraction and content determination of total flavonoids, studies on the isolation and identification of flavonoid monomers are few. Four flavonoids shown to be 78-81 were characterized from the leaves of R. laevigata. 20,21) Interestingly, 78 is flavan-3-ol and occurs in a range of plants, it is considered as the main building-block to form condensed tannins. Another two analogues, identified as 82 and 83, were reported by Li et al. 21) The structures of (+)-catechin-8-acetic acid (84) and guibourtacacidine 4-Me ether (85), assigned to be new com-  Tormentic acid β-D-glucopyranosyl ester Aerial part, Root, Fruit 1,6,7,10) 7 Tormentic acid 6-methoxy-β-D-glucopyranosyl ester Aerial part 6) 8 Euscaphate Aerial part, Fruit, Leaf, Root 6-8,10,11) 9 Euscaphic acid β-D-glucopyranosyl ester Aerial part, Root 1,6,10) 10 Oleanolic pounds, together with a known flavonoid (86), were identified by Li et al. 10) Additionally, six flavonoids isolated from R. laevigata for the first time were identified as 87-92. Importantly, 92, mainly existing in the species of Malus (Rosaceae), is useful as chemotaxonomic marker for the rosaceous plant species. 22) To date, 14 tannins (93-106) including seven new hydrolyzable tannins, laevigatins A-G (93-96, 104-106), were isolated from R. laevigata. 23,24) In general, tannins isolated from R. laevigata were dimeric ellagitannins closely related to agrimoniin (103), in whose structure, two glucose cores were linked through a dehydrodigalloyl group. For instance, chemical conversions of 101 to 93, and of 103 to 94 and 95, as well as of 96 to 102, could be achieved in the structure characterization of 93-96. Besides, the structure of 103 was finally confirmed by the partial hydrolysis of 103 with tannase to give 104.
A total of 14 lignans (107-120) have been isolated from the fruits of R. laevigata, however, only two lignans characterized as rosalaevins A-B (107 and 108), were designated as new lignans. The remain known lignans were respectively identified as 109-120 by comparison of their NMR data with those reported in the literatures. 21) Although the fruit of R. laevigata is rich in polysaccharides (approximately 260.5 mg/g), 25) few phytochemical researches have been carried out on the isolation of polysaccharides from R. laevigata till now. 121 and 122 determined to be two new selenium (Se)-containing polysaccharides, were isolated through an effective and rapid approach in which microwaveassisted aqueous two-phase extraction (MA-ATPE) with a polyethylene glycol (PEG)/ammonium sulfate system was developed. 26) Their chemical structures were determined by weight-average molecular mass, acid hydrolysis and Se-content analysis, as well as NMR spectroscopy studies. 121 was found to be mainly composed of mannose, glucose, galactose and xylose in a molar ratio of 1.4 : 7.9 : 1.0 : 1.5, while 122 was composed of mannose, rhamnose, glucose, galactose and xylose (12.6 : 1.0 : 38.3 : 5.6 : 19.6). In addition, a novel acid polysaccharide (123) with the molecular weight of 1.37 × 10 5 Da and a triple-helix conformation was purified from the pulp of R. laevigata fruit, which had 16 types of glycosidic linkages. Its primary chemical structure was characterized by monosaccharide composition, methylation, IR and NMR analysis. 27)

Pharmacology
As a medicinal and edible homologous plant, R. laevigata has been proved to have a variety of pharmacological activities both in vivo and in vitro. Table 2 summarizes the key pharmacological activities reported for this species as well as

Antioxidative Activity
The data from these antioxidant assays clearly show that multiple components of R. laevigata have good antioxidant activities against oxidative stress, and thus this edible fruit can be considered as a good source of natural antioxidants. 21,28,29) In general, flavonoids are an important part of antioxidant research on R. laevigata, but those pharmacological studies are often not limited to the superficial measurement of antioxidant capacity, so the relevant content will be presented in the following specific sections. It is noteworthy that the antioxidant capacities of lignans and brown pigment in R. laevigata are extraordinary. 21,29,30) The detailed results were summarized in Table 2.
3.2. Immunomodulation Immune stimulation is con- Fig. 2. Ursane-Type Triterpenoids Isolated from R. laevigata sidered to be an important means to improve the defence mechanism of the elderly and cancer patients. [31][32][33][34] Evidences have provided important implications of R. laevigata as an attractive immunomodulatory agent to activate the immune vitality of macrophages. In the immunomodulatory activity assays, an acid polysaccharide (123) was verified to exert the immunoregulatory activities by markedly enhancing phagocytosis, the secretion and mRNA expression of cytokines in RAW264.7 cells. 27) The mechanism of its immunoregulation is related to the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-κB) signalling pathways. 27,35,36) Specifically, the scavenger receptor (SR), glucan

Major findings
Ref.
Antioxidative activity

21)
Brown pigment It exhibited a potent radical scavenging activity, with a concentration-dependent inhibition of hydroxyl radical and superoxide free radical at low concentrations.

29)
Immunomodulation PPRLMF-2 (123) PPRLMF-2 exerted the immunoregulatory activities by markedly enhancing phagocytosis, the secretion and mRNA expression of cytokines in RAW264.7 cells; its mechanisms of action contributed to the activation of the MAPKs and NF-κB signaling pathways.

75-77
These compounds can effectively inhibit NO production induced by LPS in RAW264.7

18,19)
Whole plant extract Pretreatment of R. laevigata could remarkably attenuate allergic asthma in the chronic inflammation mice model through decreasing inflammatory cells, the secretion of IgE and related cytokines in a dose-dependent pattern.

Hepatic protection
Total flavonoids (TFs) TFs could resist liver damage caused by CCl 4 , LPS, Propionibacterium acnes, paracetamol, ischemia/reperfusion injury and high-fat diet; TFs could reduce the incidence of liver lesions, and improve liver cell DNA fragmentation and mitochondrial ultrastructure changes; the mechanisms of action involved the activation of PPARs and PGC-1α.

44-49)
Total saponins (RLTS) RLTS could protect the liver injury induced by CCl 4 through a similar mechanism of action; RLTS exerted anti-fibrotic effects via regulating the signalling pathways of TGFβ/Smad, FAK-PI3K-Akt-p70S6K and MAPKs; the realization of RLTS in matrix degradation attributed to down-regulation of MMPs; RLTS could induce autophagy and suppress inflammation to treat acetaminophen-induced liver damage.

38,50-52)
Renal protection Fruit extract R. laevigata fruit extract exerted a renal protective effect through significantly ameliorating renal dysfunction in diabetic rats; with treatment of R. laevigata, the activity of superoxide dismutase and total antioxidant capacity of kidney-damaged rodents increased while the levels of MDA and ROS reduced.

Anti-inflammation
In the anti-inflammatory study of R. laevigata, triterpenoids have received the most attention and their anti-inflammatory mechanism can mainly be attributed to inhibit the abnormal activation of NF-κB signalling pathway caused by lipopolysaccharide (LPS) and other stimulants. 8,37,38) Taking compound 21 as an instance, it exhibited moderate inhibitory activity on the release of tumour necrosis factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, and IL-10 with IC 50 values of 14.32, 8.53, 8.04, and 10.38 µM, respectively, while the IC 50 value was measured as 23.21 µM for the inhibition on NF-κB transcriptional activity. In addition, the triterpenoids derivatives from the fruit of R. laevigata var. leiocapus also exhibited promising anti-inflammatory effects. 18,19) What is more, pretreatment of R. laevigata extract could remarkably attenuate allergic airway inflammation in the chronic inflammation mice model through decreasing inflammatory cells, the secretion of immunoglobulin E (IgE) and related cytokines in a dose-dependent pattern, suggesting the possibility of R. laevigata as a therapeutic agent for allergic asthma via the modulation of IgE and related cytokines. 39) 3

.4. Hepatic Protection
The liver is the largest metabolic organ in the human body while a diverse set of toxic elements causes liver damage and diseases. [40][41][42][43] A large number of studies have shown that R. laevigata can be applied as a promising candidate of liver protection and its mechanisms of action were all related to the functions of increasing antioxidant capacity against oxidative stress by raising antioxidant enzymes, suppressing inflammation via affecting NF-κB. In general, the main components of R. laevigata on liver protection are total flavonoids (TFs) and saponins (RLTS). For instance, the protective effect of TFs against CCl 4 -induced hepatotoxicity in mice was investigated by Zhang et al. 44) Their results revealed that TFs could up-regulate the expression of B-cell lymphoma-2 (Bcl-2) and down-regulate the expressions of CYP proteins E1 (CYP2E1), inducible nitric oxide synthase (iNOS), TNF-α, NF-κB, Caspase-3, fibroblast-associated (Fas)/Fas ligand (FasL), Bcl-2-antagonist/killer (Bak) and Bcl associated X protein (Bax) to alleviate liver injury. Moreover, TFs could remarkably decrease the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice serum, while increase the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). At the same time, TFs increased the amount of glutathione (GSH) and reduced the amount of malondialdehyde (MDA). Histopathological observation also showed that TFs reduced the incidence of liver lesions, and improved liver cell DNA fragmentation and mitochondrial ultrastructure changes. It was believed that the above effect should be attributed to the activation of peroxisome proliferators-activated receptors (PPARs) and peroxysome proliferator activated receptor-γ coactlvator 1α (PGC-1α) by TFs. 45) Similar findings also included that TFs could resist liver damage caused by LPS, 46) Propionibacterium acnes, paracetamol, 47) ischemia/reperfusion injury 48) and high-fat diet. 49) In addition to TFs, RLTS could also protect the liver injury induced by CCl 4 through a similar mechanism of action. 38,50,51) Moreover, RLTS exerted anti-fibrotic effects via regulating the signalling pathways of transforming growth factor-β (TGFβ)/mothers against DPP homolog (Smad), focal adhesion kinase 1 (FAK)-phosphoinositide 3-kinase (PI3K)protein kinase B (Akt)-p70S6 Kinase (p70S6K) and MAPKs. Further research also indicated that the realization of RLTS in matrix degradation could be attributed to down-regulation of matrix metalloproteinases (MMPs). Besides, Dong et al. conducted the evaluation on the effect of RLTS against acetaminophen-induced liver damage in mice, they found that RLTS could induce autophagy and suppress inflammation to treat acetaminophen-induced liver damage. 52) 3.5. Renal Protection Traditionally, the fruit of R. laevigata is believed to possess the effects of improving sperm count and kidney health. 21) Modern pharmacological studies have demonstrated that this plant does have renal protection effects and supported their application in the ethnomedicines. 53,54) In general, R. laevigata could significantly ameliorate renal dysfunction by affecting the SIR2-like protein 1 (Sirt1)/NF-E2 related factor 2 (Nrf2)/NF-κB signalling pathway as oxidative stress, inflammation and apoptosis were found to be associated with the disease renal injury. 55,56) With treatment of R. laevigata, the activity of superoxide dismutase and total antioxidant capacity of kidney-damaged rodents increased while the levels of MDA and reactive oxygen species (ROS) reduced. More importantly, the research disclosed that the effect of the plant extract against renal injury depended on Sirt1.
3.6. Cardiovascular and Cerebrovascular Protection Cardiovascular and cerebrovascular disease is the leading cause of death in the world. 57) The effects of R. laevigata on cardiovascular and cerebrovascular protection are mainly attributed to flavonoids due to their anti-apoptotic, antioxidant and anti-inflammatory properties. [58][59][60] For instance, Liu et al. found oral administration of TFs with high-dose led to the decreases of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), while the increase of high density lipoprotein-cholesterol (HDL-C). 61) Jia et al. 62) proved the protective effect of TFs against the damage of human umbilical vein endothelial cells induced by hydrogen peroxide. Zhang et al. 63) found that oral administration of flavonoid-rich extract (FRE) from R. laevigata significantly improved the survival rate and obviously prevented cerebral ischemia-reperfusion (I/R) induced disability and histopathological damage. Additionally, the antithrombotic effects of TFs were reported by Zhang et al. that oral administration of TFs could markedly reduce the whole blood viscosity, platelet aggregation, along with prolong thrombin and prothrombin time of rats in the acute blood stasis model induced by ice water and adnephrin. 64) 3.7. Neuroprotection Oxidative stress-induced neuronal death plays an important role in the pathogenesis of neurodegenerative diseases, 65) suggesting R. laevigata could be developed as a potential candidate for neuroprotection. TFs from R. laevigata has been showed to exhibit a good effect on H 2 O 2 -induced oxidative damage of nerve cells owing to its protection against cell apoptosis, DNA and mitochondrial damage. 66) Additionally, the polysaccharide (121) showed obvious neuroprotective activity by relieving oxidative stress in SH-SY5Y neuroblastoma cells, 26) while two polyhydroxy triterpenoids (14 and 22) were proved to show acetylcholines-terase (AChE) inhibitory activity and neuroprotective effects against H 2 O 2 -induced SHSY5Y cell death. 17) In particular, 14 and 22 caused a 92 and 89% inhibition on the target enzyme at high concentration, which was consistent with the results in AChE molecular docking studies.

Improvement of Diabetic Cataract
More and more evidences suggested that abnormal ROS metabolism may be an important factor leading to diabetic cataract. [67][68][69] Liu et al. investigated the effects of R. laevigata extract (RLE) on ROS production and matrix metalloproteinases (MMPs) in lens epithelial cells cultured under high glucose condition. The results revealed the RLE treatment to exert protective effects on SRA01/04 cells, and the mechanism of action is to reduce the production of ROS and increase the level of MMPs by affecting PI3K/Akt and Nrf2/antioxidant response element (ARE) signalling pathways. 70) Although there are few pharmacological studies on the treatment of diabetic cataract, it also indirectly indicates that R. laevigata has multiple pharmacological effects.

Conclusion
R. laevigata is a kind of medicine and food homologous plant that has been used for a long time. The present review summarizes this medicinal plant comprehensively from the aspects of photochemistry and pharmacology. To date, previous studies on phytochemical investigation in various parts of R. laevigata have exposed the presence of triterpenoids, flavonoids, tannins, ligands and polysaccharides in this plant. Among these isolates (123 ingredients in total), 77 triterpenoids have been isolated and thus regarded to be main and characteristic substance of this plant, and could be taken as typical chemotaxonomic markers for identification of R. laevigata from the phytochemical point of view. Currently, the obtained triterpenoids can be divided into four categories based on their structures: ursane-type (totaling 45 compounds), oleanane-type (totaling 13 compounds), lupinane-type (totaling 8 compounds), as well as seco-triterpenoids (totaling 11 compounds). In general, most of the triterpenoids obtained from R. laevigata can be classified into polyhydroxy triterpenoids, the main differences among them depended on the number of the hydroxyl groups and their substitution positions. Most of the pharmacological researches on R. laevigata are mainly focused on its fruits while other tissues such as leaf, stems and roots have received relatively less attention. According to the literature reports, R. laevigata exhibited antioxidant activity, immunomodulatory effect, anti-inflammatory effect, liver protection, kidney protection, cardiovascular protection, neuroprotective effect, and improvement of diabetic cataract. Interestingly, these pharmacological results provide evidences to prove the correlations between folk medication experience and pharmacological activity research, for example, R. laevigata has been regarded as a valuable kidney tonifying medicinal diet, while modern pharmacological studies show that R. laevigata can significantly improve renal insufficiency by regulating Sirt1/Nrf2/NF-κB signalling pathway. 56) In addition, these different chemical ingredients existing in the title plant may have synergistic effects. For instance, both TFs and RLTS from R. laevigata could exert the liver protective effects through increasing the body's antioxidant capacity as well as suppressing inflammation and apoptosis. [44][45][46][47][48][49][50][51][52] In conclusion, pharmacological studies on crude extracts and chemical ingre-dients of R. laevigata have revealed this plant to be a valuable source for therapeutic foodstuff.

Future Perspective
Although considerable progress has been made in the phytochemistry and pharmacology of R. laevigata, there are still some important areas to be explored in order to better understand its pharmacological effects and clinical efficacy. (i) Till now, pharmacological studies on the title plant have mainly focus on the total flavonoids, and thus the evidence of medicinal value of other types of compounds is still lacking, especially triterpenoids, which have been proved to be the dominant substances existing in R. laevigata. Consequently, the pharmacological researches of other components should be strengthened to support their application in ethnic medicine. (ii) The evaluation of biological activities of R. laevigata are principally focus on anti-inflammatory and anti-oxidation actions, and even other pharmacological studies were carried out around these two factors. Hence the in-depth mechanism of action remains to be investigated with modern pharmacological techniques. (iii) Toxicological studies of R. laevigata are limited. The current data only provide study on subchronic toxicity of total flavonoids from R. laevigata fruit at oral doses of 500, 1000 and 2000 mg/kg/d in rats. In the high dose group, the decreased adrenal gland weight and platelet counts, along with the increased intercellular space of myocardial cells and the relative heart weight were observed, therefore, the dose of 500 mg/kg/d was considered as noobserved-adverse-effect-level. 71) However, the toxicity of other components has not been reported, hence, extensive toxicity and safety assessment should be conducted to determine the side effects, acute and chronic toxicity. (iv) Obviously, triterpenoids (especially ursane-type triterpenes) are the principal and characteristic bioactive substances occurring in this species. However, polysaccharides have been documented as the standard for the quality control of R. laevigata in Chinese Pharmacopoeia (2020 Edition). According to our opinion, total triterpenoids should be considered as new standard in the new version of Chinese Pharmacopoeia. (v) In literature review, it was found that there were few studies on chemistry and pharmacology which were consistent with the efficacy of traditional Chinese medicine theory of R. laevigata. Above all, let's take the best-known efficacy of R. laevigata, renal protective and fertility-improving function, as an example. In traditional Chinese medicine theory, the fruit of R. laevigata is believed to possess the effects of improving sperm count and kidney health. Although it has been reported that the fruits of this plant could protect the kidney through affecting the Sirt1/Nrf2/NF-κB signaling pathway, articles focus on this aspect are still scarce, and the animal models used are not diversified. Moreover, to the best of our knowledge, there is no report on the improvement of sexual dysfunction by this plant. More importantly, to date, there is no single monomer compound has been proved to be responsible for these efficacies. In addition, during the investigation on the pharmacological researches in this plant, most of the activities could be attributed to the antioxidant and anti-inflammatory activities. Therefore, appropriate experimental models in vivo and in vitro should be selected pertinently in future research in order to better combine the pharmacological activities with the traditional medication experience. Additionally, specific monomer compounds should be demonstrated to be responsible for the studied pathological models. To be emphasized once again, the in-depth mechanism of action remains to be investigated with modern pharmacological techniques.