• Journal of Ginseng Research
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• v.44 no.5
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• Korean Journal of Pharmacognosy
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• v.47 no.1
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• pp.73-78
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• 2016

The purpose of this study is to develop a new preparation process of ginseng (Panax ginseng) flower buds extracts featuring high concentration of ginsenosides Rg2, Rg3, Rg5, F4 and Rh1, red ginseng special components. Chemical transformation from ginseng saponin glycosides to prosapogenin was analyzed by the HPLC. Extracts of ginseng flower buds were processed under several treatment conditions of ultrasonication (at $100^{\circ}C$). The results showed that the quantity of ginsenoside Rg6 increased by over 8.8% at the 16 hours of ultrasonication. Ginseng flower buds ethanol extract compared with other process times. The result of UGF-16 indicates that the ultrasonication processed ginseng flower buds extracts (at $100^{\circ}C$) treated for 16 hours produced the highest amount of ginsenoside F4 (8.833%), Rg3 (2.230%), Rg5 (2.339%) and Rg2 (1.002%).

• Journal of Ginseng Research
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• v.37 no.2
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• pp.219-226
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• 2013

This study was conducted to investigate the effect of extrusion conditions (moisture content 20% and 30%, screw speed 200 and 250 rpm, barrel temperature $115^{\circ}C$ and $130^{\circ}C$) on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng (KRG). Extruded KRGs showed relatively higher amounts of acidic polysaccharide (6.80% to 9.34%) than non-extruded KRG (4.34%). Increased barrel temperature and screw speed significantly increased the content of acidic polysaccharide. The major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg2s, Rg3s, Rh1, and Rg3r) of KRG increased through extrusion, while the ginsenoside (Rg1) decreased. The EX8 (moisture 30%, screw speed 250 rpm, and temperature $130^{\circ}C$) had more total phenolics and had a better scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals than those of extruded KRG samples. The extrusion cooking showed a significant increase (6.8% to 20.9%) in reducing power. Increased barrel temperature significantly increased the values of reducing power, the highest value was 1.152 obtained from EX4 (feed moisture 20%, screw speed 250 rpm, and temperature $130^{\circ}C$). These results suggest that extrusion conditions can be optimized to retain the health promoting compounds in KRG products.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.108-116
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• 2013

For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG ($19.14{\pm}0.50$ mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, $11.31{\pm}1.15$ mg/g). The antioxidant activities in FRG, such as 2,2'-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were $41.65{\pm}1.53$ mg/g and $50.12{\pm}1.43$ mg/g, respectively. However, FRG had a significantly higher content ($33.90{\pm}0.97$ mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG ($14.75{\pm}0.46$ mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

• Molecules and Cells
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• v.21 no.1
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• pp.52-62
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• 2006

In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent $Ca^{2+}$ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned $Ca^{2+}$ channel subtypes such as ${\alpha}_{1C}$(L)-, ${\alpha}_{1B}$(N)-, ${\alpha}_{1A}$(P/Q)-, ${\alpha}_{1E}$(R)- and ${\alpha}_{1G}$(T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on $Ba^{2+}$ currents ($I_{Ba}$) in Xenopus oocytes expressing five different $Ca^{2+}$ channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the ${\alpha}_{1G}$-type. Of the various ginsenosides, $Rb_1$, Rc, Re, Rf, $Rg_1$, $Rg_3$, and $Rh_2$, ginsenoside $Rg_3$ also inhibited all five channel subtypes and ginsenoside $Rh_2$ had most effect on the ${\alpha}_{1C}$- and ${\alpha}_{1E}$-type $Ca^{2+}$ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the ${\alpha}_{1G}$-type of $Ca^{2+}$ channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. $Rg_3$, $Rh_2$, and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the ${\alpha}_{1B}$- and ${\alpha}_{1A}$-types. These results reveal that $Rg_3$, $Rh_2$ and CK are the major inhibitors of $Ca^{2+}$ channels in Panax ginseng, and that they show some $Ca^{2+}$ channel selectivity.

• Food Science and Biotechnology
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• v.18 no.2
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• pp.513-518
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• 2009

This study was carried out to investigate the changes of yield, total phenolics, saponin content and composition, antimicrobial, and antioxidant activities of various fractions of fine ginseng root (Panax ginseng C.A. Mayer) by maceration method in the order of increasing polarity (hexane, chloroform, ethyl acetate, butanol, and water). Butanol fraction showed the highest total saponin content compare to other fractions. Hexane fraction could harvest significantly high ginsenoside Rg2, Rg1, and Rf (p<0.05). And the contents of ginsenoside Rh1, Rg3, and Rg1 showed relatively higher in the fraction of ethyl acetate than other fractions. The system of hexane-chloroform-ethyl aceate-butanol showed relatively high content of ginsenoside Re, Rd, Rc, Rb3, and Rb1. However, the last fraction of water still remained lots of Rb2 content. The fraction of water was the highest phenolics. The 1,1-diphenyl-2-picryhydrazil, superoxide, and hydroxyl radical scavenging activity of water fraction was higher than the other fractions. In antimicrobial activity, the fraction of hexane showed relatively high antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Bacillus cereus, and Escherichia coli. And the fractions of the chloroform and ethyl acetate showed higher antimicrobial activities than the other samples in against P. aeruginosa and S. typhimurium.

• Journal of Ginseng Research
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• v.36 no.4
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• pp.425-429
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• 2012

In this study, hydroponically-cultivated ginseng leaves, fruits, and roots were respectively extracted with ethanol. The contents of 12 ginsenosides and three phenolics in the extracts were quantitatively analyzed and the free radical scavenging activities were measured and compared. Hydroponically-cultivated ginseng leaves contained higher levels of gensenosides (Rg1, Rg2+Rh1, Rd, and Rg3) and p-coumaric acid than the other parts of the ginseng plants. The 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid radical scavenging activities of leaves were also the highest. Accordingly, hydroponically-grown ginseng leaves were shown to hold promise for use as an environmentally-friendly natural anti-oxidant.

• Journal of Life Science
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• v.26 no.2
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• pp.247-252
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• 2016

Cultivated wild ginseng is a widely used dietary supplement and medicinal herb. The aim of this study was to optimize the ginseng using high performance liquid chromatography (HPLC)- charged aerosol detection (CAD) for ginsenoside analysis. CAD measures the physical property of an analyte and responds to almost all non-volatile species, independent of their nature, spectral properties, or particle size. It has become widely employed in pharmaceutical analysis. The cultivated wild ginseng extracts were analyzed for compositions of ginsenosides Rb1, Rd, Rg1, Rf, Re, and Rh1. The optimal analysis condition was set up from an experiment using a gradient. Ten grams of cultivated wild ginseng were extracted with 95% EtOH 100 ml for 24 hr at 80℃. The contents of the 6six major ginsenosides in the cultivated wild ginseng extract were Rb1 (5.48±0.12 mg/g), Rd (5.33±0.14 mg/g), Rg1 (12.80± 0.05 mg/g), Rf (19.08±0.68 mg/g), Re (19.87±0.05 mg/g), and Rh1 (16.47±0.16 mg/g), respectively. HPLC showed that the protopanaxatriol group (Rg1, Rf, Re, Rh1) had more content than the protopanaxadiol group (Rb1, Rd) in cultivated wild ginseng extract. In summary, the ginsenosides were identified with HPLC-CAD analysis, and their presence and quantity imply the importance of quality control, as well as the pharmacological activity of the ginseng root.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2010.10a
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• pp.20-20
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• 2010

Panax ginseng C.A Meyer is frequently taken orally as a traditional herbal medicine in Asian countries. The major components of ginseng are ginsenoside, which are pharmaceutical activity. The six major ginsenosides, including Rb1, Rb2, Rc, Rd, Re and Rg1 account for 90% of total ginsenosides. Even though the minor ginsenosides, including Rg3, Rh2 and compound K has high pharmacetical activities, the price of minor ginsenosides is too high. Therefore we isolated the gypenoside V and made it converted to minor ginsenosides. In the plant Gynostemma pentaphyllum Makino, gypenosdie V was presented as dominant saponin (content about 2.4%), and was similar to protopanaxadol type ginsenosides such as ginsenoside Rb1. In this study, we confirmed that the coversion of gypenoside V to minor ginsenosides after using the various treatment such as heating, acid treatment, commercial edible enzyme, and lactobacillus. Consequently, we optimizied the transformation of gypenoside V to minor ginsenoside using Thin Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC), Time-of-flight Mass Spectrometry (LC/TOF/MS).