• Journal of Ginseng Research
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• v.41 no.1
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

• Journal of Microbiology and Biotechnology
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• v.27 no.9
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• pp.1559-1565
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• 2017

Naturally occurring ginsenoside F1 (20-O-${\beta}$-$\text\tiny{D}$-glucopyranosyl-20(S)-protopanaxatriol) is rare. Here, we produced gram-scale quantities of ginsenoside F1 from a crude protopanaxatriol saponin mixture comprised mainly of Re and Rg1 through enzyme-mediated biotransformation using recombinant ${\beta}$-glucosidase (BgpA) cloned from a soil bacterium, Terrabacter ginsenosidimutans Gsoil $3082^T$. In a systematic step-by-step process, the concentrations of substrate, enzyme, and NaCl were determined for maximal production of F1. At an optimized NaCl concentration of 200 mM, the protopanaxatriol saponin mixture (25 mg/ml) was incubated with recombinant BgpA (20 mg/ml) for 3 days in a 2.4 L reaction. Following octadecylsilyl silica gel column chromatography, 9.6 g of F1 was obtained from 60 g of substrate mixture at 95% purity, as assessed by chromatography. These results represent the first report of gram-scale F1 production via recombinant enzyme-mediated biotransformation.

• Mycobiology
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• v.42 no.3
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• pp.256-261
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• 2014

A ${\beta}$-glucosidase producing yeast strain was isolated from Korean traditional rice wine. Based on the sequence of the YCL008c gene and analysis of the fatty acid composition, the isolate was identified as Saccharomyces cerevisiae strain HJ-014. S. cerevisiae HJ-014 produced ginsenoside Rd, $F_2$, and compound K from the ethanol extract of red ginseng. The production was increased by shaking culture, where the bioconversion efficiency was increased 2-fold compared to standing culture. The production of ginsenoside $F_2$ and compound K was time-dependent and thought to proceed by the transformation pathway of: red ginseng extract ${\rightarrow}Rd{\rightarrow}F_2{\rightarrow}$ compound K. The optimum incubation time and concentration of red ginseng extract for the production of compound K was 96 hr and 4.5% (w/v), respectively.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.213-218
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• 1996

Multidrug resistance (MDR) has been a major problem in cancer chemotherapy. To overcome this problem, we prepared minor ginsenosides stereoselectively from ginseng saponins and searched for a ginseng component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of several ginseng components, 20(S)-ginsenoside Rg_3$, a red ginseng saponin, was found to have the most potent inhibitory activity on MDR and it's concentration capable of inhibiting 50% growth was $82\muM$.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.324-331
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• 2013

Channels formed by the co-assembly of the KCNQ1 subunit and the mink (KCNE1) subunit underline the slowly activating delayed rectifier $K^+$ channels ($I_{Ks}$) in the heart. This $K^+$ channel is one of the main pharmacological targets for the development of drugs against cardiovascular disease. Panax ginseng has been shown to exhibit beneficial cardiovascular effects. In a previous study, we showed that ginsenoside Rg3 activates human KCNQ1 $K^+$ channel currents through interactions with the K318 and V319 residues. However, little is known about the effects of ginsenoside metabolites on KCNQ1 $K^+$ alone or the KCNQ1 + KCNE1 $K^+$ ($I_{Ks}$) channels. In the present study, we examined the effect of protopanaxatriol (PPT) and compound K (CK) on KCNQ1 $K^+$ and $I_{Ks}$ channel activity expressed in Xenopus oocytes. PPT more strongly inhibited the $I_{Ks}$ channel currents than the currents of KCNQ1 $K^+$ alone in concentration- and voltage-dependent manners. The $IC_{50}$ values on $I_{Ks}$ and KCNQ1 alone currents for PPT were $5.18{\pm}0.13$ and $10.04{\pm}0.17{\mu}M$, respectively. PPT caused a leftward shift in the activation curve of $I_{Ks}$ channel activity, but minimally affected KCNQ1 alone. CK exhibited slight inhibition on $I_{Ks}$ and KCNQ1 alone $K^+$ channel currents. These results indicate that ginsenoside metabolites show limited effects on $I_{Ks}$ channel activity, depending on the structure of the ginsenoside metabolites.

• Journal of Ginseng Research
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• v.33 no.3
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• pp.206-211
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• 2009

In order to investigate the effects of elicitors on the growth and ginsenoside biosynthesis of ginseng hairy roots, we treated Panax ginseng hairy root with various concentrations of Haliotidis concha according to different time course. Haliotidis concha supplement increased the biomass and ginsenoside accumulation at 10 mg/L concentration. The growth rate of hairy root under a lighter concentration was greater than hairy root treated with a denser concentration. The highest content and productivity of ginsenosides appeared at 2 weeks after the treatment of 10 mg/L Haliotidis concha. The gene expression of squalene synthase, squalene epoxidase, dammarenediol synthase, cycloartenol synthase, $\beta$-amyrin synthase in hairy roots of ginseng were examined by RT-PCR. The Haliotidis concha treatment resulted in the obvious accumulation of the mRNA of triterpene biosynthesis in Panax ginseng hairy root as compared with the control. In this study, Haliotidis concha acts as a kind of elicitor for the production of ginsenosides.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1087-1094
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• 2009

The purpose of this study was investigated hypoglycemic effects of fermented red ginseng extracts. We prepared non-fermented red ginseng extracts(R), fermented with Lactobacillus plantarum(RL) extracts, Saccharomycescerevisiae(RS) extracts, and L. plantarum mixed S. cerevisiae(RLS) extracts, examined composition of ginsenosides, SOD-like activity, and $\alpha$-glucosidase inhibitory activity. Ginsenoside Re was highest contents in all extracts, second was ginsenoside Rc and then ginsenoside Rb1. Concentration of these ginsenoside was showed higher in RS than in other extracts. SOD-like activity and $\alpha$-glucosidase inhibitory activity were shown higher in fermented red ginseng extracts than non fermented extracts. And activities of mixed fermentation extracts(RLS) higher than single fermentation extracts(RL, RS). Effects of blood glucose level, serum lipid profile and metabolic variables were evaluated in streptozotocin(STZ) induced diabetic rat. Experimental group was divided into 7 groups: normal control group(hereafter NC group), diabetes control group(DC group), positive control group treated with 50 mg/kg body weight of acarbose(PC group), treated with 300 mg/kg body weight of R, RL, RS and RLS extracts groups, respectively. Blood glucose level of DC group was maintained high level in all experimental period, but treated with red ginseng extracts groups was reduced the glucose level by R group 18.00%, RL group 28.07%, RS group 29.03%, RLS group 42.42%, respectively. The concentration of total cholesterol and triglyceride of fermented red ginseng extracts treated groups (RL, RS, RLS) was lower than non- fermented extracts group(R) DC and PC groups. The activity of ALT, AST in RLS treated groups were lower than other groups.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6191-6196
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• 2012

Aims and Background: Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside $Rg_1$ ($Rg_1$), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether $Rg_1$ can induce cancer cell senescence is still unclear. Methods: In the current study, human leukemia K562 cells were subjected to $Rg_1$ exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of $Rg_1$ on cell cycle were analyzed using flow cytometry and by SA-${\beta}$-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. Results: K562 cells demonstrated a maximum proliferation inhibition rate with an $Rg_1$ concentration of $20{\mu}\;mol{\cdot}L^{-1}$ for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-${\beta}$-galactosidase (SA-${\beta}$-Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin $G_2$/M phase after $Rg_1$ interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Conclusion: Ginsenoside $Rg_1$ can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.

• Korean Journal of Plant Resources
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• v.18 no.1
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• pp.123-130
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• 2005

High salt concentrations in the ginseng nursery soil environment of Korea is one of important reducing factors for the stable production of quality ginseng. These studies were accomplished for check the response on germination of ginseng seed, somatic embryogenesis of zygotic embryo, and biosynthesis of ginsenoside from ginseng hairy root against NaCl. Ratio of germination was at the $3\%\;and\;84.5\%$ on the basic media with 0.1M and free of NaCl repectedly, but $0\%$ at the upper of 0.2M NaCl. Somatic embryogenesis from zygotic embryo were the highest when immatured embryo was cultured on free of NaCl concentration, and which was intend to decrease at treatment of NaCl. However, in case of using the matured embryo, treatment of 0.05M NaCl resulted in better embryogenesis than NaCl free media. Red pigment was synthesized from ginseng hairy root cultured on the medium with various NaCl concentration(from 0.04 to 0.08M) and its pigment was analyzed as spectrum of anthocyane by spectrophoto- meter scanning. This cell line biosynthesized lots of crude saponin and total ginsenoside than other cell lines, also had 2 times of panaxadiol than panaxatriol.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.11
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• pp.1660-1665
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• 2010

To obtain data for the standardization of manufacturing method of red ginseng extract pouch products, saponin and physico-chemical properties of 44 Korean red ginseng extract pouch products were analyzed. The concentration of total ginsenoside contents were 5.5~185.7 mg/100 mL. Distribution of the contents of ginsenoside $Rg_3$, $Rg_2$, $Rh_1$, and $Rh_2$ known to have anticancer effect are as follows: $Rg_3$ is 1.6~46.3 mg/100 mL, $Rg_2$ is 0~22.0 mg/100 mL, $Rh_1$ is 0~4.3 mg/100 mL and that of $Rh_2$ is 0~20.4 mg/100 mL, respectively. The anti-diabetic effect of ginsenoside $Rb_2$ and Re distribution of contents were 0~10.8 mg/100 mL and 0~7.0 mg/100 mL, respectively. Among the other saponins, exhibited content to distribution of ginsenoside $Rb_1$ was 0~25.2 mg/100 mL, Rc was 0~12.5 mg/100 mL, Rd was 0~11.3 mg/100 mL, Rf was 0~5.9 mg/100 mL and $Rg_1$ was 0~4.4 mg/100 mL. Results of physicochemical characterization showed total sugar content of 226.6~3,102.9 mg/100 mL, total soluble solids content $1.4\sim9.5^{\circ}Bx$, turbidity 82.2~100.0%, pH in the range of 4.1 to 5.0, respectively. In approximately 50% of collected domestic ginseng extract pouch products (21~24 items), ginsenoside $Rb_1$, $Rb_2$, Rc, Rd, Re and $Rg_1$ were not detected, and saponin content of each product appears to differ greatly. Results indicated that standardization of production methods and standards set for red ginseng extract pouch products in Korea is needed.