• Journal of Ginseng Research
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• v.47 no.2
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.636-645
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• 2022

Background: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity. Methods: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results: Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells. Conclusion: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.524-530
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• 2017

Background: Panax ginseng is a physiologically active plant widely used in traditional medicine that is characterized by the presence of ginsenosides. Rb1, a major ginsenoside, is used as the starting material for producing ginsenoside derivatives with enhanced pharmaceutical potentials through chemical, enzymatic, or microbial transformation. Methods: To investigate the bioconversion of ginsenoside Rb1, we prepared kimchi originated bacterial strains Leuconostoc mensenteroides WiKim19, Pediococcus pentosaceus WiKim20, Lactobacillus brevis WiKim47, Leuconostoc lactis WiKim48, and Lactobacillus sakei WiKim49 and analyzed bioconversion products using LC-MS/MS mass spectrometer. Results: L. mesenteroides WiKim19 and Pediococcus pentosaceus WiKim20 converted ginsenoside Rb1 into the ginsenoside Rg3 approximately five times more than Lactobacillus brevis WiKim47, Leuconostoc lactis WiKim48, and Lactobacillus sakei WiKim49. L mesenteroides WIKim19 showed positive correlation with b-glucosidase activity and higher transformation ability of ginsenoside Rb1 into Rg3 than the other strains whereas, P. pentosaceus WiKim20 showed an elevated production of Rb3 even with lack of b-glucosidase activity but have the highest acidity among the five lactic acid bacteria (LAB). Conclusion: Ginsenoside Rg5 concentration of five LABs have ranged from ${\sim}2.6{\mu}g/mL$ to $6.5{\mu}g/mL$ and increased in accordance with the incubation periods. Our results indicate that the enzymatic activity along with acidic condition contribute to the production of minor ginsenoside from lactic acid bacteria.

• Journal of Ginseng Research
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• v.23 no.1 s.53
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• pp.50-54
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• 1999

In this paper, the saponin enzymatic hydrolysis of ginsenoside Rg3 was studied. The $ginsenoside-{\beta}-glucosidase$ from FFCDL-48 strain mainly hydrolyzed the ginsenoside Rg3 to Rh2, the enzyme from FFCDL-00 strain hydrolyzed Rg3 to the mixture of Rh2 and protopanaxadiol (aglycon). The $ginsenoside-{\beta}-glucosidase$ from FFCDL-48 strain was purified with a column of DEAE-Cellulose to one spot in the SDS polyacrylamide gel electrophoresis. During the purification, the enzyme specific acitvity was increased about 10 times. The purified $ginsenoside-{\beta}-glucosidase$ can hydrolyze the Rg3 to Rh2, but do not hydrolyze the $p-nitrophenyl-{\beta}-glucoside$ which is a substrate of original exocellulase such as ${\beta}-glucosidase$ of cellulose. The molecular weight of $ginsenoside-{\beta}-glucosidase$ was 34,000, the optimal temperature of enzyme reaction was $50^{\circ}C,$ and the optimal pH was 5.0.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.286-290
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• 2011

Ginsenoside Rg3 was reported to have important biological activities. We demonstrate conjugation and quantification procedures of ginsenoside Rg3 to gold nanoparticles for future biological and medical applications. Ginsenoside Rg3 was conjugated to spherical gold nanoparticles using a bifunctional heptaethylene glycol linker. The sulfhydryl group of heptaethylene glycol was adsorbed onto gold nanoparticles, and carboxylic acid end of heptaethylene glycol was bonded through a hydroxyl group of Rg3 via ester bond formation. The conjugation of Rg3 was characterized with various spectroscopic techniques, high resolution-transmission electron microscopy, and using Rg3 monoclonal antibody. The Rg3- functionalized gold nanoparticles were $4.7{\pm}1.0$ nm in diameter with a surface charge of -4.12 mV. The total number of Rg3 molecules conjugated to a 3.6 mL solution of gold nanoparticle was determined to be $9.5{\times}10^{14}$ corresponding to ~6 molecules of Rg3/gold nanoparticle. These results suggest that ginsenoside Rg3 is successfully conjugated to gold nanoparticles via heptaethylene glycol linker. The quantification was performed by using Rg3 monoclonal antibody without interference of gold's intrinsic color.

• Journal of Ginseng Research
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• v.33 no.3
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• pp.183-188
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• 2009

To produce ginsenoside-Rg$_3$ enriched edible yeast, ginseng steaming effluent (GSE) was used for yeast cultivation in this study. Four kinds of edible yeasts were cultured in sterilized GSE (2% w/v, pH 6.5), without any nutrient, for 48 h at 30$^{\circ}C$, and their growth and ginsenoside compositions were determined. Among the yeasts, Saccharomyces cerevisiae showed the highest growth in the GSE medium. 267.1 mg of Saccharomyces cerevisiae biomass was produced from 1 g of GSE solid and ginsenoside-Rg$_3$ contents was determined with 0.033 mg. Saccharomyces cerevisiae also showed the best overall acceptability, with a herbal and fermentative flavor and a slightly bitter taste. From these data, we conclude that Saccharomyces cerevisiae is the excellent strain for production of ginsenoside-Rg$_3$ enriched edible yeast using GSE.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.78-84
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• 2017

Background: In the present study, metabolite profiles of ginsenosides Rk1 and Rg5 from red ginseng or red notoginseng in zebrafish were qualitatively analyzed with ultraperformance liquid chromatography/quadrupole-time-of-flight MS, and the possible metabolic were pathways proposed. Methods: After exposing to zebrafish for 24 h, we determined the metabolites of ginsenosides Rk1 and Rg5. The chromatography was accomplished on UPLC BEH C18 column using a binary gradient elution of 0.1% formic acetonitrile-0.1% formic acid water. The quasimolecular ions of compounds were analyzed in the negative mode. With reference to quasimolecular ions and MS2 spectra, by comparing with reference standards and matching the empirical molecular formula with that of known published compounds, and then the potential structures of metabolites of ginsenosides Rk1 and Rg5 were acquired. Results: Four and seven metabolites of ginsenoside Rk1 and ginsenoside Rg5, respectively, were identified in zebrafish. The mechanisms involved were further deduced to be desugarization, glucuronidation, sulfation, and dehydroxymethylation pathways. Dehydroxylation and loss of C-17 residue were also metabolic pathways of ginsenoside Rg5 in zebrafish. Conclusion: Loss of glucose at position C-3 and glucuronidation at position C-12 in zebrafish were regarded as the primary physiological processes of ginsenosides Rk1 and Rg5.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.132-140
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• 1997

The effects of ginsenosides purified from red ginseng on platelet aggregation were investigated. Preincubation of washed platelets from rats with either ginsenoside Rg3, ginsenosides non-polar fraction (G-NPF), ginsenoside Rg1(Rg1) or ginsenosides polar fraction(G-PF) reduced the plytelet aggrelation induced by collagen in a dose-dependent manner, whereas ginsenoside Rg2 failed to inhibit the aggregation. Their IC50 values of Rg3, G-NPF, Rgl, and G-PF were 8.7$\pm$1.0, 150.3$\pm$0.1, 369.9$\pm$ 1.0, 606.211.3 $\mu\textrm{g}$/ml, respectively. Aggrelation induced by thrombin was also inhibited by Rg3 and G-NPF with IC50 being 5.2$\pm$ 1.1 and 66.5$\pm$0.8 $\mu\textrm{g}$/ml, respectively. The alterations of Intracellular Ca2+ concentration in platelets were monitored using fura-2 as a fluorescent Ca2+ indicator. Both Ca2+ release from internal stores and Ca2+ influx into cytosol were suppressed by Rg3. Rg3 also inhibited granular release of ATP and TXA2 formation induced by thrombin in a dose-dependent manner in the washed platelets. Rg3 also inhibited Aggregation and ATP release from human platelets induced by collagen to a similar extent as were observed in rat platelets. In conclusion, Rg3 is a Potent anti-aggregating component in ginsenosides and may exert its anti-aggrega1ing activity by decreasing TXAa formation and granular secretion in platelets, most likely by inhibiting Ca2+ influx and Ca2+ mobilization from intracellular stores. Thus ginseng may contribute to the prevention and treatment of thrombosis.

• Korean Journal of Pharmacognosy
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• v.45 no.4
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• pp.320-325
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• 2014

The purpose of this study is to develop a new preparation process of Notoginseng root(Panax notoginseng) extracts having high concentrations of ginsenoside $Rg_3$, $Rg_5$, $Rk_1$ and $Rh_4$, a special component of Red and Black ginseng(Panax ginseng). Chemical transformation from ginseng saponin to prosapogenin was analyzed by the HPLC. Extracts of Notoginseng root was processed under several treatment conditions including microwave and vinegar(about 14% acidity) treatments. Results of those treatments showed that the quantity of ginsenoside $Rg_3$ increased by over 7.6% at 15 minutes of pH 2~4 vinegar and microwave treatments. The results of processing with MPN-15 indicate that the microwave and vinegar(about 14% acidity) processed Notoginseng root extracts that had gone through 15-minute treatments were found to contain the largest amount of ginsenoside $Rg_3$(7.639%), $Rg_5$(6.061%), $Rk_1$(1.516%) and $Rh_4$(1.599). It is thought that such results provide basic information in preparing Notoginseng root extracts with functionality enhanced.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1136-1140
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• 2004

Red ginseng and fermented red ginseng were prepared, and their composition of ginsenosides and antiischemic effect were investigated. When ginseng was steamed at 98-$100{\circ}C$ for 4h and dried for 5h at $60{\circ}C$, and extracted with alcohol, its main components were ginsenoside $Rg_3$ > ginsenoside $Rg_1$> ginsenoside $Rg_2$. When the ginseng was suspended in water and fermented for 5 days by previously cultured Bifidobacterium H-1 and freeze-dried (fermented red ginseng), its main components were compound K > ginsenoside $Rg_3{\geq}$ ginsenoside $Rg_2$. Orally administered red ginseng extract did not protect ischemia-reperfusion brain injury. However, fermented red ginseng significantly protected ischemica-reperfusion brain injury. These results suggest that ginsenoside Rh2 and compound K, which was found to be at a higher content in fermented red ginseng than red ginseng, may improve ischemic brain injury.