• Journal of Ginseng Research
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• v.44 no.4
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• pp.664-671
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• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.221-229
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• 2015

Background: Minor ginsenosides, those having low content in ginseng, have higher pharmacological activities. To obtain minor ginsenosides, the biotransformation of American ginseng protopanaxadiol (PPD)-ginsenoside was studied using special ginsenosidase type-I from Aspergillus niger g.848. Methods: DEAE (diethylaminoethyl)-cellulose and polyacrylamide gel electrophoresis were used in enzyme purification, thin-layer chromatography and high performance liquid chromatography (HPLC) were used in enzyme hydrolysis and kinetics; crude enzyme was used in minor ginsenoside preparation from PPD-ginsenoside; the products were separated with silica-gel-column, and recognized by HPLC and NMR (Nuclear Magnetic Resonance). Results: The enzyme molecular weight was 75 kDa; the enzyme firstly hydrolyzed the C-20 position 20-O-${\beta}$-D-Glc of ginsenoside Rb1, then the C-3 position 3-O-${\beta}$-D-Glc with the pathway $Rb1{\rightarrow}Rd{\rightarrow}F2{\rightarrow}C-K$. However, the enzyme firstly hydrolyzed C-3 position 3-O-${\beta}$-D-Glc of ginsenoside Rb2 and Rc, finally hydrolyzed 20-O-L-Ara with the pathway $Rb2{\rightarrow}C-O{\rightarrow}C-Y{\rightarrow}C-K$, and $Rc{\rightarrow}C-Mc1{\rightarrow}C-Mc{\rightarrow}C-K$. According to enzyme kinetics, $K_m$ and $V_{max}$ of Michaelis-Menten equation, the enzyme reaction velocities on ginsenosides were Rb1 > Rb2 > Rc > Rd. However, the pure enzyme yield was only 3.1%, so crude enzyme was used for minor ginsenoside preparation. When the crude enzyme was reacted in 3% American ginseng PPD-ginsenoside (containing Rb1, Rb2, Rc, and Rd) at $45^{\circ}C$ and pH 5.0 for 18 h, the main products were minor ginsenosides C-Mc, C-Y, F2, and C-K; average molar yields were 43.7% for C-Mc from Rc, 42.4% for C-Y from Rb2, and 69.5% for F2 and C-K from Rb1 and Rd. Conclusion: Four monomer minor ginsenosides were successfully produced (at low-cost) from the PPD-ginsenosides using crude enzyme.

• Korean Journal of Pharmacognosy
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• v.26 no.4
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• pp.360-367
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• 1995

The metabolism of ginseng saponins by human intestinal bacteria was studied using human feces under anaerobic culture conditions. $Ginsenoside-Rb_1$, $-Rb_2$ and -Rc(protopanaxadiol type) were mainly metabolized to compound-K(C-K), $20-O-[{\alpha}-L-arabinopyranosyl(1{\rightarrow}6)-{\beta}-{_D}-glucopyranosyl]-20(S)-protopanaxadiol(compound-Y,\;C-Y)$, $20-O-[{\alpha}-L-arabinopyranosyl(1{\rightarrow}6)-{\beta}-{_D}-glucopyranosyll-20(S)-protopanaxadiol(ginsenosied-MC,{\;}MC)$, respectively, and $ginsenoside-Rg_1$ and -Re(protopanaxatriol type) to their aglycon, 20(S)-protopanaxatriol, though the pathway and rate of the metabolism were affected by fermentation medium. C-K was not decomposed any more, while C-Y and Mc were both gradually hydrolyzed to C-K.

• BMB Reports
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• v.44 no.10
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• pp.659-664
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• 2011

As part of the search for biologically active anti-osteoporotic agents that enhance differentiation and mineralization of osteoblastic MC3T3-E1 cells, we identified the ginsenoside Rh2(S), which is an active component in ginseng. Rh2(S) stimulates osteoblastic differentiation and mineralization, as manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and Alizarin Red staining, respectively. Rh2(S) activates p38 mitogen-activated protein kinase (MAPK) in time- and concentration-dependent manners, and Rh2(S)-induced differentiation and mineralization of osteoblastic cells were totally inhibited in the presence of the p38 MAPK inhibitor, SB203580. In addition, pretreatment with Go6976, a protein kinase D (PKD) inhibitor, significantly reversed the Rh2(S)-induced p38 MAPK activation, indicating that PKD might be an upstream kinase for p38 MAPK in MC3T3-E1 cells. Taken together, these results suggest that Rh2(S) induces the differentiation and mineralization of MC3T3-E1 cells through activation of PKD/p38 MAPK signaling pathways, and these findings provide a molecular basis for the osteogenic effect of Rh2(S).

• Journal of Ginseng Research
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• v.40 no.4
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• pp.366-374
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• 2016

Background: In this study, we screened and identified an endophyte JG09 having strong biocatalytic activity for ginsenosides from Platycodon grandiflorum, converted ginseng total saponins and ginsenoside monomers, determined the source of minor ginsenosides and the transformation pathways, and calculated the maximum production of minor ginsenosides for the conversion of ginsenoside Rb1 to assess the transformation activity of endophyte JG09. Methods: The transformation of ginseng total saponins and ginsenoside monomers Rb1, Rb2, Rc, Rd, Rg1 into minor ginsenosides F2, C-K and Rh1 using endophyte JG09 isolated by an organizational separation method and Esculin-R2A agar assay, as well as the identification of transformed products via TLC and HPLC, were evaluated. Endophyte JG09 was identified through DNA sequencing and phylogenetic analysis. Results: A total of 32 ${\beta}$-glucosidase-producing endophytes were screened out among the isolated 69 endophytes from P. grandiflorum. An endophyte bacteria JG09 identified as Luteibacter sp. effectively converted protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, Rd into minor ginsenosides F2 and C-K, and converted protopanaxatriol-type ginsenoside Rg1 into minor ginsenoside Rh1. The transformation pathways of major ginsenosides by endophyte JG09 were as follows: $Rb1{\rightarrow}Rd{\rightarrow}F2{\rightarrow}C-K$; $Rb2{\rightarrow}C-O{\rightarrow}C-Y{\rightarrow}C-K$; $Rc{\rightarrow}C-Mc1{\rightarrow}C-Mc{\rightarrow}C-K$; $Rg1{\rightarrow}Rh1$. The maximum production rate of ginsenosides F2 and C-K reached 94.53% and 66.34%, respectively. Conclusion: This is the first report about conversion of major ginsenosides into minor ginsenosides by fermentation with P. grandiflorum endophytes. The results of the study indicate endophyte JG09 would be a potential microbial source for obtaining minor ginsenosides.

• Herbal Formula Science
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• v.30 no.3
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• pp.175-182
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• 2022

Objective : This study aims to investigate the active ingredients and potential mechanisms of the beneficial herb on human cancers such as the liver by employing network pharmacology. Methods : Ingredients and their target information was obtained from various databases such as TM-MC, TTD, and Drugbank. Related protein for liver cancer was retrieved from the Comparative Toxicogenomics Database and literature. A hypergeometric test and gene set enrichment analysis were conducted to evaluate associations between protein targets of red ginseng (Panax ginseng C. A. Meyer) and liver cancer-related proteins and identify related signaling pathways, respectively. Network proximity was employed to identify active ingredients of red ginseng on liver cancer. Results : A compound-target network of red ginseng was constructed, which consisted of 363 edges between 53 ingredients and 121 protein targets. MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, TGF-beta signaling pathway, and cell cycle pathway was significantly associated with protein targets of red ginseng. Network proximity results indicated that Ginsenoside Rg1, Acetic Acid, Ginsenoside Rh2, 20(R)-Ginsenoside Rg3, Notoginsenoside R1, Ginsenoside Rk1, 2-Methylfuran, Hexanal, Ginsenoside Rd, Ginsenoside Rh1 could be active ingredients of red ginseng against liver cancer. Conclusion : This study suggests that network-based approaches could be useful to explore potential mechanisms and active ingredients of red ginseng for liver cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.90-90
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• 2020

Panax ginseng C.A. Meyer (P. ginseng) is known to exert a wide range of pharmacological effects both in vitro and in vivo. Although studies on ginsenoside, antioxidant activity, and anticancer effect of wild simulated ginseng (WSG) have been conducted, there is little research on the effect of WSG on bone metabolism. In this study, we investigated the potential anti-osteoporotic properties of WSG on the growth and differentiation of MC3T3-E1 cells. WSG significantly increased the viability and proliferation of MC3T3-E1 cells. WSG activated intracellular alkaline phosphatase (ALP) activity in MC3T3-E1 cells. In addition, WSG increased the mineralized nodules in MC3T3-E1 cells. Furthermore, WSG increased the expression of genes such as Runx2, ALP, OPN and OCN associated with osteoblast growth and differentiation in a dose-dependent manner.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.199-207
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• 2018

Background: Ginseng is a well-known traditional Chinese medicine that has been widely used in a range of therapeutic and healthcare applications in East Asian countries. Microbial transformation is regarded as an effective and useful technology in modification of nature products for finding new chemical derivatives with potent bioactivities. In this study, three minor derivatives of ginsenoside compound K were isolated and the inducing effects in the Wingless-type MMTV integration site (Wnt) signaling pathway were also investigated. Methods: New compounds were purified from scale-up fermentation of ginsenoside Rb1 by Paecilomyces bainier sp. 229 through repeated silica gel column chromatography and high pressure liquid chromatography. Their structures were determined based on spectral data and X-ray diffraction. The inductive activities of these compounds on the Wnt signaling pathway were conducted on MC3T3-E1 cells by quantitative real-time polymerase chain reaction analysis. Results: The structures of a known 3-keto derivative and two new dehydrogenated metabolites were elucidated. The crystal structure of the 3-keto derivative was reported for the first time and its conformation was compared with that of ginsenoside compound K. The inductive effects of these compounds on osteogenic differentiation by activating the Wnt/b-catenin signaling pathway were explained for the first time. Conclusion: This study may provide a new insight into the metabolic pathway of ginsenoside by microbial transformation. In addition, the results might provide a reasonable explanation for the activity of ginseng in treating osteoporosis and supply good monomer ginsenoside resources for nutraceutical or pharmaceutical development.

• Advances in Traditional Medicine
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• v.6 no.4
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• pp.286-292
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• 2006

In this study, we evaluated the antiproliferative effects of Panax notoginseng, ginsenoside Rb1, and notoginsenoside R1 in the human breast carcinoma MCF-7 cell line. Our results indicated that both Panax notoginseng radix extract (NRE) and Panax notoginseng rhizoma extract (NRhE) possess significant antiproliferative activities in MCF-7 cells. Compared to control group (100%), at the concentrations of 0.05, 0.5, and 1.0 mg/ml NRE, cell growth was concentration-dependently reduced to 81.0 ${\pm}$ 6.1 (P < 0.01), 34.2 ${\pm}$ 4.8 (P < 0.001), and 19.3 ${\pm}$ 1.9 (P < 0.001), respectively. Similar results with NRhE at concentrations of 0.5 and 1.0 mg/ml were obtained in these MCF-7 cells. To identify the responsible chemical constituent, we tested the antiproliferation effects of two representative saponins, ginsenoside Rb1 and notoginsenoside R1, on the MCF-7 cells. The data showed that ginsenoside Rb1 was endowed with antiproliferative properties, while notoginsenoside R1 did not have an inhibitory effect in the concentrations tested. Our studies provided evidence that Panax notoginseng extracts and ginsenoside Rb1 may be beneficial, as adjuvants, in the treatment of human breast carcinoma.

• Journal of Ginseng Research
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• v.28 no.4
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• pp.165-172
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• 2004

Ginseng is traditionally cultivated worldwide in cold continental climates. It is now also being cultivated in maritime environments such as New Zealandis. This paper reports a number of growth and quality parameters for plants grown under those conditions over two growing seasons and the intervening winter dormant period. While shoot biomass peaked mid-summer, in contrast, root biomass peaked late autumn/early winter. Starch, sucrose, fructose, glucose and inositol were detected in the roots. Starch concentrations were highest in early autumn (mean 470 mg $g^{-1}$ dry weight) and lowest in mid spring (218 mg $g^{-1}$ dry weight). Sucrose concentrations were low during early summer until late autumn but increased rapidly with the onset of winter and peaked during mid spring (168 mg $g^{-1}$ dry weight). Fructose and glucose concentrations were similar and peaked in late spring (5.3 and 6.2 mg $g^{-1}$ dry weight). Inositol concentrations peaked in mid summer (1.7 mg $g^{-1}$ dry weight). Starch/sugar ratios were high during summer and autumn and low during winter and spring. Ginsenoside concentrations and profiles showed that the six major ginsenosides, Rgl, Re, Rb1, Rc, Rb2 and Rd, were present, but Rf was absent. Concentrations did not vary with sampling date. The most abundant ginsenosides were Re (15.9 to 17.5 mg $g^{-1}$ dry weight) and Rb1 (10.7 to 18.1 mg $g^{-1}$ dry weight). Combined, they accounted for < $75{\%}$ of total ginsenoside concentrations. Limited taste tests indicated that highest root quality occurred during late autumn, after the shoots had senesced. However, quality could not be related to plant chemistry.