• Journal of Ginseng Research
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• v.39 no.4
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• pp.287-298
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• 2015

Ginseng, a perennial plant belonging to the genus Panax of the Araliaceae family, is well known for its medicinal properties that help alleviate pathological symptoms, promote health, and prevent potential diseases. Among the active ingredients of ginseng are saponins, most of which are glycosides of triterpenoid aglycones. So far, numerous saponins have been reported as components of Panax ginseng, also known as Korean ginseng. Herein, we summarize available information about 112 saponins related to P. ginseng; >80 of them are isolated from raw or processed ginseng, and the others are acid/base hydrolysates, semisynthetic saponins, or metabolites.

• Journal of Ginseng Research
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• v.29 no.1
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• Korean Journal of Pharmacognosy
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• v.49 no.2
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• pp.85-102
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• 2018

A drug interaction is a situation in which a substance affects the activity of a drug, synergistically or antagonistically, when both are administered together. It has been shown that orally taken ginsenosides are deglycosylated by intestinal bacteria to give ginsenosides metabolites, which has been considered to be genuine pharmacological constituents and to exhibit drug interactions. Animal experimental results demonstrated that ginsenoside metabolites play an important role in the inhibitory or inductive action of both CYPs (cytochrome p450) and P-gp (p-glycoprotein), thereby can be applied as metabolic modulator to drug interactions. Very few are known on the possibility of drug interaction if taken the recommended dose of ginseng, but it has been found to act as CYPs inductor and P-gp inhibitor in any clinical trial, suggesting the risk that side effects will occur. It has been recently reported that interactions might also exist between ginseng and drugs such as warfarin, phenelzine, imatinib and raltegravir. Moreover, medicinal plants are increasingly being taken in a manner more often associated with prescription medicines. Therefore, considering the extensive applications of ginseng for safety, the aim of this review is to present a comprehensive overview of ginseng and drug interactions based upon pharmacodynamic and pharmacokinetic evidences.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.293-299
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• 2013

20S-dihydroprotopanaxadiol (2H-PPD) is a derivative of protopanaxadiol, a glycone of ginsenosides prepared from Panax ginseng. Although ginsenosides and acidic polysaccharides are known to be major active ingredients in ginseng, the immunopharmacological activities of their metabolites and derivatives have not been fully explored. In this study, we aimed to elucidate the regulatory action of 2H-PPD on the function of monocytes and macrophages in innate immune responses. 2H-PPD was able to boost the phagocytic uptake of fluorescein isothiocyanate-dextran in macrophages and enhance the generation of radicals (reactive oxygen species) in sodium nitroprusside-treated RAW264.7 cells. The surface levels of the costimulatory molecules such as CD80 and CD86 were also increased during 2H-PPD treatment. In addition, this compound boosted U937 cell-cell aggregation induced by CD29 and CD43 antibodies, but not by cell-extracellular matrix (fibronectin) adhesion. Similarly, the surface levels of CD29 and CD43 were increased by 2H-PPD exposure. Therefore, our results strongly suggest that 2H-PPD has the pharmacological capability to upregulate the functional role of macrophages/monocytes in innate immunity.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.461-474
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• 2020

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Journal of Applied Biological Chemistry
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• v.52 no.1
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• pp.21-27
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• 2009

Red ginseng (RG) and fermented red ginseng (FRG) are produced from ginseng (GS) via certain biological processes. The main difference between three ginsengs is the composition of ginsenosides known as major metabolites having several biological activities. The concentration of the metabolites has been known to be dependent on the methods which make RG and FRG In this study, we investigated the effects of WG, RG and FRG on the productions of inflammatory proteins (NF-${\kappa}B$, iNOS, COX-2) and cytokines (TNF-$\alpha$, INF-$\gamma$) in LPS-stimulated RAW 264.7 cells. The levels of NO production and iNOS expression were suppressed by the treatment of white ginseng (WG), RG and FRG in LPS-stimulated cells. Also, the production of TNF-$\alpha$ and INF-$\gamma$ was decreased in the cells by all of them. It was indicated that the inhibition of NF-${\kappa}B$ activation in LPS-stimulated cells treated with three kinds of ginsengs was resulted from the suppression of the level of COX-2 expression and the phosphorylation of IkB by LPS. The present study indicated that RC showed the best biological activity among them and FRG was better than WG. The better activity of RG on the inhibition of NO production is considered to be caused by the difference of ginsenoside composition produced during their preparations. In order to elucidate the mechanism, animal test should be performed with three ginsengs.

• Korean Journal of Medicinal Crop Science
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• v.22 no.1
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• pp.17-22
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• 2014

Ginsenosides of roots in Panax ginseng were analyzed by metabolic-targeting HPLC using the partial least squares discriminant analysis (PLS-DA) and compared depending on sowing methods between direct seeding and transplanting method. Score plots derived from PLS-DA could identify the sowing method between the direct seeding and transplanting method in P. ginseng roots. The ginsenoside compounds were assigned as Rg1, Re, Rf, Rg2, Rb1, Rc, Rb2, Rb3, and Rd. Contents of Re, Rf, Rg2, Rb1, Rc, Rb3, and Rd of main roots produced from the transplanting method were relatively higher than those of samples produced from direct seeding method. Also, contents of Rg1, Re, Rf, Rg2, Rb1, Rc, Rb2, Rb3, and Rd of lateral roots from the transplanted samples were relatively higher than those of samples produced from direct seeding method. Therefore, HPLC with PLS-DA analysis can be a straightforward tool for identification of ginsenosides in main or lateral roots of P. ginseng obtained from two different seeding methods between direct and transplanting methods.

• Journal of Ginseng Research
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• v.20 no.4
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• pp.389-415
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• 1996

Panax ginseng C.A. Meyer(Araliaceae) has been traditionally used as an expensive and precious medicine in oriental countries for more than 5, 000 years. Ginseng saponin isolated from the root of Panax ginseng have been regarded as the main effective components responsible for the pharmacological and biological activities. Such as antiaging effects. antidiabetic effects anticancer effects. Protection against physical and chemical stress. Analgesic and antipyretic effects. Effects on the central nervous system, tranquilizing action and others. Thirty kinds of ginsenosides have been so far isolated from ginseng saponin and their chemical structures have been elucidated since 1960's. Among which protopanaxadiol type is 19 kinds. protopanaxatriol type. 10 kinds and oleanane type, one. Since ginsenosides are generally labile under acidic conditions ordinary acid hydrolysis is always accompanied by many side reactions, such as epimerization. hydroxylation and cyclization of side chain of the sapogenins Especially. it is well known that C-20 glycosyl linkage of ginsenoside was hydrolysed on heating with acetic acid to give an equilibrated mixture of 20(S) and 20(R) epimers. And also, the chemical transformations of the secondary metabolites have appeared during the steaming process to prepare red ginseng. Indicating demalonylation of malonyl ginsenosides, elimination of glycosyl residue at C-20 and isomerization of hydroxyl configuration at C-20. But these studies have not provided a comprehensive picture in explaning how these ginsenosides showed val'iotas pharmacological activities of ginseng. Though some of them have been involved in the mechanism of pharmacological actions. Recently, non-saponin components have received a great deal of attention for their antioxidant, anticancer antidiabetic, immunomodulating. anticomplementary activities and so on. To meet the demand for such wide applications, studies on the non-saponin components play an important role in providing a good evidence of pharmacological and biol ogical activities. Among the non-saponin constituents of Korean ginseng, polyacetylenes, phenols. Sesquiterpenes, alkaloids. polysaccharides oligosaccharides, oligopeptides and aminoglycosides together with ginsenosides of terrestrial part are mainly described.