• Proceedings of the Ginseng society Conference
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• 2004.12a
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• pp.7-11
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• 2004

We previously reported that ginseng inhibited NMDA receptors in cultured hippocampal neurons. Here, we further examined the detailed mechanism of ginseng-mediated inhibition using its main active ingredient, ginsenoside Rg$_3$. Co-application of ginsenoside Rg$_3$ with increasing concentrations of NMDA did not change the EC$_{50}$ of NMDA to the receptor, suggesting ginsenoside Rg$_3$ inhibits NMDA receptors without competing with the NMDA-binding site. Ginsenoside Rg$_3$-mediated inhibition also occurred in a distinctive manner from the well-characterized NMDA receptor open channel blocker, MK-801, However, ginsenoside Rg$_3$ produced its effect in a glycine concentration-dependent manner and shifted the glycine concentration-response curve to the right without changing the maximal response, suggesting the role of ginsenoside Rg$_3$ as a competitive NMDA receptor antagonist. We also demonstrated that ginsenoside Rg$_3$ significantly protected neurons against NMDA insults. Therefore, these results suggest that ginsenoside Rg$_3$ protects NMDA-induced neuronal death via a competitive interaction with the glycine-binding site of NMDA receptors in cultured hippocampal neurons.

• Journal of Microbiology and Biotechnology
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• v.16 no.11
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• pp.1791-1798
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• 2006

When ginsenoside Rg5, a main component isolated from red ginseng, was incubated with three human fecal microflora for 24 h, all specimens showed hydrolyzing activity: all specimens produced ginsenoside Rh3 as a main metabolite, but a minor metabolite $3{\beta},12{\beta}$-dihydroxydammar-21(22),24-diene (DD) was observed in two specimens. To evaluate the antiallergic effect of ginsenoside Rg5 and its metabolites, the inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 against RBL-2H3 cell degranulation, mouse passive cutaneous anaphylaxis (PCA) reaction induced by the IgE-antigen complex, and mouse ear skin dermatitis induced by 12-O-tetradecanoilphorbol-13-acetate (TPA) were measured. Ginsenosides Rg5 and Rh3 potently inhibited degranulation of RBL-2H3 cells. These ginsenosides also inhibited mRNA expression of proinflammatory cytokines IL-6 and $TNF-{\alpha}$ in RBL-2H3 cells stimulated by IgE-antigen. Orally and intraperitoneally administered ginsenoside Rg3 and orally administered ginsenoside Rg5 to mice potently inhibited the PCA reaction induced by IgE-antigen complex. However, intraperitoneally administered ginsenoside Rg5 nearly did not inhibit the PCA reaction. These ginsenosides not only suppressed the swelling of mouse ears induced by TPA, but also inhibited mRNA expression of cyclooxygenase-2, $TNF-{\alpha}$, and IL-4 and activation of transcription factor NF-kB. These inhibitions of ginsenoside Rh3 were more potent than those of ginsenoside Rg5. These findings suggest that ginsenoside Rg5 may be metabolized in vivo to ginsenoside Rh3 by human intestinal microflora, and ginsenoside Rh3 may improve antiallergic diseases, such as rhinitis and dermatitis.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.304-313
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• 2015

Background: Ginsenoside Rg3 is a promising anticancer agent. It is usually produced by heat treatment of ginseng, in which ginsenoside Rb1 is the major ginsenoside. A kinetic study was conducted to optimize ginsenoside Rg3 production by the heat treatment of ginsenoside Rb1. Methods: Ginsenoside Rb1 was heated using an isothermal machine at $80^{\circ}C$ and $100^{\circ}C$ and analyzed using HPLC. The kinetic parameters were calculated from the experimental results. The activation energy was estimated and used to simulate the process. The optimized parameters of ginsenoside Rg3 production are suggested based on the simulation. Results: The rate constants were $0.013h^{-1}$ and $0.073h^{-1}$ for the degradation of ginsenosides Rb1 and Rg3 at $80^{\circ}C$, respectively. The corresponding rate constants at $100^{\circ}C$ were $0.045h^{-1}$ and $0.155h^{-1}$. The estimated activation energies of degradation of ginsenosides Rb1 and Rg3 were 69.2 kJ/mol and 40.9 kJ/mol, respectively. The rate constants at different temperatures were evaluated using the estimated activation energies, and the kinetic profiles of ginsenosides Rb1 and Rg3 at each temperature were simulated based on the proposed kinetic model of consecutive reaction. The optimum strategies for producing ginsenoside Rg3 from ginsenoside Rb1 are suggested based on the simulation. With increased temperature, a high concentration of ginsenoside Rg3 is formed rapidly. However, the concentration decreases quickly after the reaching the maximal concentration value. Conclusion: The optimum temperature for producing ginsenoside Rg3 should be the highest temperature technically feasible below $180^{\circ}C$, in consideration of the cooling time. The optimum reaction time for heat treatment is 30 min.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.685-690
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• 2006

The effect of a main constituent ginsenoside Rg5 isolated from red ginseng and its metabolite ginsenoside Rh3 in a chronic dermatitis model was investigated. Ginsenosides Rg5 and Rh3 suppressed swelling of oxazolone-induced mouse ear contact dermatitis. These ginsenosides also reduced mRNA expressions of cyclooxygenase-2, interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$ and interferon $(IFN)-{\gamma}$. The inhibition of ginsenoside Rh3 was more potent than that of ginsenoside Rg5. These findings suggest that ginsenoside Rh3 metabolized from ginsenoside Rg5 may improve chronic dermatitis or psoriasis by the regulation of $IL-1{\beta}$ and $TNF-{\alpha}$ produced by macrophage cells and of $IFN-{\gamma}$ produced by Th cells.

• Journal of Ginseng Research
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• v.32 no.3
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• pp.264-269
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• 2008

Ginsenosides are major components in Panax ginseng and known to have numerous pharmacological activities such as anti-cancer, anti-diabetes, anti-viral and anti-atherosclerosis effects. In this study, the regulatory activities of G-Rg3 and its derivative 25-hydroxy Rg3 (G-Rg3-2H) on the production of nitric oxide (NO) in macrophages and the proliferation of lymphocytes prepared from spleen and bone marrow under treatment of lipopolysaccharide (LPS) or concanavalin (Con) A were examined. G-Rg3 and G-Rg3-2H dose-dependently inhibited NO production from LPS-activated RAW264.7 cells and in agreement, these compounds protected RAW264.7 cells from LPS-mediated cytotoxicity. In contrast, G-Rg3-2H dose-dependently inhibited lymphocyte proliferation induced by both LPS and Con A, while there was no inhibition by G-Rg3. Therefore, our data suggest that these compounds may be applied for NO-mediated or lymphocyte-mediated immunological diseases.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.61-67
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• 2004

When ginseng water extract was incubated at $60^{\circ}C$ in acidic conditions, its protopanaxadiol ginsenosides were transformed to ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$. However, protopanaxadiol glycoside ginsenosides $Rb_1, Rb_2$ and Rc isolated from ginseng were mostly not transformed to ginsenoside $Rg_3$ by the incubation in neutral condition. The transformation of these ginsenosides to ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$ was increased by increasing incubation temperature and time in acidic condition: the optimal incubation time and temperature for this transformation was 5 h and $60^{\circ}C$ resepectively. The transformed ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$ were metabolized to ginsenoside $Rh_2$ and $\Delta^{20}$--ginsenoside $Rh_2$, respectively, by human fecal microflora. Among the bacteria isolated from human fecal microflora, Bacteroides sp., and Bifidobacterium sp. and Fusobacterium sp. potently transformed ginsenoside $Rg_3$ to ginsenoside $Rh_2$. Acid-treated ginseng (AG) extract, fermented AG extract, ginsenoside $Rh_2$ and protopanaxadiol showed potent cytotoxicity against tumor cell lines. AG extract, fermented AG extract and protopanaxadiol potently inhibited the growth of Helicobacter pylori.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.654-664
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• 2021

Background: Ginsenoside Rg3, isolated from Panax ginseng, has anti-inflammatory and anti-tumor activities. It is known to reduce inflammation in acute lung injury in mice, and to reduce the expression of inflammatory cytokines and COX-2 in human asthmatic airway epithelium. In this study, we attempted to determine whether ginsenoside Rg3 inhibits airway inflammation, oxidative stress, and airway hyperresponsiveness (AHR) in the lungs of asthmatic mice. We also investigated its effects on oxidative stress and the inflammatory response in tracheal epithelial cells. Methods: Asthma symptoms were induced in female BALB/c mice sensitized with ovalbumin (OVA). Mice were divided into five groups: normal controls, OVA-induced asthmatic controls, and asthmatic mice treated with ginsenoside Rg3 or prednisolone by intraperitoneal injection. Inflammatory BEAS-2B cells (human tracheal epithelial cells) treated with ginsenoside Rg3 to investigate its effects on inflammatory cytokines and oxidative responses. Results: Ginsenoside Rg3 treatment significantly reduced eosinophil infiltration, oxidative responses, airway inflammation, and AHR in the lungs of asthmatic mice. Ginsenoside Rg3 reduced Th2 cytokine and chemokine levels in bronchoalveolar lavage fluids and lung. Inflammatory BEAS-2B cells treated with ginsenoside Rg3 reduced the eotaxin and pro-inflammatory cytokine expressions, and monocyte adherence to BEAS-2B cells was significantly reduced as a result of decreased ICAM-1 expression. Furthermore, ginsenoside Rg3 reduced the expression of reactive oxygen species in inflammatory BEAS-2B cells. Conclusion: Ginsenoside Rg3 is a potential immunomodulator that can ameliorate pathological features of asthma by decreasing oxidative stress and inflammation

• YAKHAK HOEJI
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• v.35 no.5
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• pp.432-437
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• 1991

A mixture of 20(R)- and 20(S)-ginsenoside Rg$_{3}$ was obtained under mild acidic hydrolysis from protopanaxadiol saponins, ginsenosides Rb$_{1}$, Rb$_{2}$, Rc and Rd. The product was acetylated to give the peracetates, which were further converted into 20(R)-ginsenoside Rg$_{3}$, 20(S)-ginsenoside Rg$_{3}$, 20(R)-ginsenoside Rh$_{2}$ and 20(S)-ginsenoside Rh$_{2}$ by the direct alkaline treatment depending upon two kinds of temperature conditions respectively. The structure and physicochemical properties of a prosapogenin, 20(R)-ginsenoside Rh$_{2}$, were investigated.

• Journal of Ginseng Research
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• v.29 no.3
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• pp.119-125
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• 2005

The previous reports demonstrated that ginseng saponins, active ingredient of Panax ginseng, inhibited blood vessel contraction induced by various hormones or high $K^+$. Recently, we demonstrated that 20(R)- and 20(S)-ginsenoside $Rg_3$. regulate ion channel activities with differential manners. The aim of this study was to examine whether ginsenoside $Rg_3$ isomers also show differential effects on swine coronary artery contractionresponses induced by high $K^+$, serotonin (5-HT) or acetylcholine. Treatment of 20(S)- but not 20(R)-ginsenoside $Rg_3$ caused a concentration-dependent relaxation of coronary artery contracted by 25mM KCI. 20(S)- and 20(R)-ginsenoside $Rg_3$ induced significant relaxations of coronary artery contraction induced by 5-HT $(3{\mu}M)$ in the presence of endothelium with concentration-dependent manner and, also in the absence of endothelium only 20(S)-ginsenoside $Rg_3$ induced a strong Inhibition of coronary artery contraction induced by 5-HT in a concentration-dependent manner. 20(S)-ginsenoside $Rg_3$ caused relaxation of coronary artery in the absence and presence of endothelium. In contrast, treatment of 20(S)- and 20(R)-ginsenoside $Rg_3\;(100{\mu}M)$ did not show significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the presence of endothelium, whereas both isomers caused significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the absence of endothelium in a concentration-dependent manner. These findings indicate that 20(S)-or 20(R)-ginsenoside $Rg_3$ exhibits differential relaxation eff3cts of swine coronary artery contractions caused by high $K^+$, acetylcholine, and 5-HT treatment and that this differential vasorelaxing effects of ginsenoside $Rg_3$ isomers also might be dependent on endothelium.

• Mycobiology
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• v.38 no.2
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• pp.153-155
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• 2010

To produce ginsenoside-$Rg_3$ enriched yeast from ginseng-steaming effluent (GSE), Lipomyces starkeyi, which tends to grow well in GSE, was cultured in sterilized GSE and its growth and production of ginsenoside-$Rg_3$ were determined. Growth of L. starkeyi was 86.1 mg per g GSE and its ginsenoside-$Rg_3$ contents was 0.013 mg per g GSE.