• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Journal of Plant Biology
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• v.39 no.1
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• pp.63-69
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• 1996

A hairy root clone of Panax ginseng C.A. Meyer, HRB-15 was cultured iu various conditions with 3 L bubble type bioreactor to enhance both growth and ginsenoside production. The hairy roots were more rapidly grown under the dark condition than under the light condition. However, total amount of ginsenoside of hairy roots cultured under the light for 30 days increased 2 folds as compared with the dark condition and was 1.10% based on 6 ginsenosides. Especially, ginsenoside-Re was significantly increased and some ginsenosides except for ginsenoside-Re was slightly reduced. Also, the growth of hairy roots decreased about 30% as compared with the dark condition. In contrast, addition of sodium acetate led to decreased production of ginsenoside and growth of hairy roots under light condition. The influence of potassium dihydrogenphosphate concentration was examined in MS medium and a 1.25 mM concentration was found to be the most appropriate for growth and ginsenoside production under light condition. Two-step process of hairy roots culture with yeast elicitation or without ammonia in culture medium was developed to enhance growth and giusenoside synthesis. $50\;\mu\textrm{g}$ of yeast elicitor per g of fresh weight showed a synergistic effect on the ginsenoside synthesis of hairy roots on 20 days after culture. At that time, the content of total ginsenoside was 1.15%, while the growth of hairy roots decreased 21 % as compared with the dark condition. In addition, when elimination of ammonia on 20 days after culture, the content of total ginsenoside was 1.26% with significant increment of ginsenoside-Rd (0.27%) in addition to ginsenoside-Re and the growth of hairy roots decreased 10% as compared with the dark condition. In this system, we have demonstrated a unique two-step process of hairy root cultures to maximize biomass and secondary metabolites. It has found possibility to enhance ginsenosides production by growing hairy roots in this method.

• 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.40 no.2
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• pp.121-126
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• 2016

Background: Ginsenoside F1, a pharmaceutical component of ginseng, is known to have antiaging, antioxidant, anticancer, and keratinocyte protective effects. However, the usage of ginsenoside F1 is restricted owing to the small amount found in Korean ginseng. Methods: To enhance the production of ginsenoside F1 as a 10 g unit with high specificity, yield, and purity, an enzymatic bioconversion method was developed to adopt the commercial enzyme Cellulase KN from Aspergillus niger with food grade, which has ginsenoside-transforming ability. The proposed optimum reaction conditions of Cellulase KN were pH 5.0 and $50^{\circ}C$. Results: Cellulase KN could effectively transform the ginsenosides Re and Rg1 into F1. A scaled-up biotransformation reaction was performed in a 10 L jar fermenter at pH 5.0 and $50^{\circ}C$ for 48 h with protopanaxatriol-type ginsenoside mixture (at a concentration of 10 mg/mL) from ginseng roots. Finally, 13.0 g of F1 was produced from 50 g of protopanaxatriol-type ginsenoside mixture with $91.5{\pm}1.1%$ chromatographic purity. Conclusion: The results suggest that this enzymatic method could be exploited usefully for the preparation of ginsenoside F1 to be used in cosmetic, functional food, and pharmaceutical industries.

• Journal of Ginseng Research
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• v.20 no.3
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• pp.241-247
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• 1996

The effects of ginseng total saponin, ginsenoside-Rb, and -Rb, on the reduction of chmlesterol level and the myNA expression rates of HMG CoA reductase and LDL receptor in Hep G2 were investigated and compared with that of lovastatin, a competitive HMG CoA reductase Inhibitor. The amounts of cholesterol in Hep G2 decreased in total saponin-and ginsenoside-treated groups as compared with that of control group, while there was no significant reduction in lovastatin-treated group. The mRNA expression rates of HMG CoA reductase increased in total saponin and gin- senoside groups except for ginsenoside-Rb, (10-3%) group and decreased in lovastatin group com- pared with that of control group. The mRNA expression rates of LDL receptor generally increased In all of the test groups except for total saponin (10-5%) group compared with that of control group. Because the ginseng components tested were more effective in the reduction of cholesterol level in Hep G2 than lovastatin and induced the gene expression of LDL receptor, we suggest the possibility that they could be used as a replacement agent for lovastatin which can not be prescribed especially to patients with hepatic diseases.

• 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.24 no.3
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• pp.134-137
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• 2000

Spontaneous bursting activity was studied in rat thalamocortical slices using extracellular field potential recording to test the potential utilization of ginsenoside Rb$_1$ in controlling overactivated neural systems. In order to induce bursting activity, slices were perfused with Mg$\^$2+/-free artificial cerebrospinal fluid (ACSF). Two major types of spontaneous bursting activity, simple thalamocortical burst complexes (sTBCs) and complex thalamocortical burst complexes (cTBCs), were recorded in Mg$\^$2+/ -free ACSF. Ginsenoside Rb$_1$ selectively suppressed cTBCs. Duration and occurrence rate of cTBCs were reduced by 87.3${\pm}$10.2% and 85.3${\pm}$ 14.7% in the presence of 90 ${\mu}$M ginsenoside Rb$_1$ respectively, while amplitude and intraburst frequency were slightly changed by ginsenoside Rb$_1$. In contrast, ginsenoside Rb$_1$was much less effective in reducing duration and occurrence rate of sTBCs. We also tested effects of ginsenoside Rb$_1$ on bursting activity in the presence of a GABA$\sub$A/ receptor antagonist, bicuculline methiodide (BMI). Ginsenoside Rb$_1$ had no effect in suppressing BMI-induced bursting activities. These results suggest that ginsenoside Rbi may be useful in controlling seizure-like bursting activity under pathological conditions.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.734-743
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• 2021

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer. Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess total and gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR, dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependent manner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cells and enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancer cells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundance significantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation and growth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression. Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.96-112
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• 2002

In the present study, we have investigated the effects of centrally administered ginsenoside Rc or Rgl on the modulation of NMDA receptor and $GABA_A$ receptor binding in rat brain. The NMDA receptor binding was analyzed by quantitative autoradiography using $[^3H]MK-801$ binding, and $GABA_A$ receptor bindings were analyzed by using $[^3H]muscimol\;and\;[^3H]flunitrazepam$ in rat brain slices. Rats were infused with ginsenoside Rc or Rg1 ($10\;{\mu}g/10{\mu}l/hr$, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML), The levels of $[^3H]MK-801$ binding were highly decreased in part of cortex and cingulated by ginsenoside Rc and Rgl. The levels of $[^3H]muscimol$ binding were strongly elevated in almost all regions of frontal cortex by the treatment of ginseoside Rc but decreased by ginsenoside Rg 1. However, the $[^3H]flunitrazepam$ binding was not modulated by ginsenoside Rc or ginsenoside Rgl infusion. These results suggest that prolonged infusion of ginsenoside could differentially modulate $[^3H]MK-801\;and\;[^3H]muscimol$ binding in a region-specific manner. Also, we investigated the influence of centrally administered ginsenoside on the regulation of mRNA levels of the family of NMDA receptor subtypes (NR1, NR2A, NR2B, NR2C) by in situ hybridization histochemistry in the rat brain. The level of NR1 mRNA is significantly increased in temporal cortex, caudate putamen, hippocampus, and granule layer of cerebellum in Rgl-infused rats as compared to control group. The level of NR2A mRNA is elevated in the frontal cortex. In contrast, it was decreased in CAI area of hippocampus in Rgl-infused rats. However, there was no significant change of NR1 and NR2A mRNA levels in Rc-infused rats. The level of NR2B mRNA is elevated in cortex, caudate putamen, and thalamus in both Rc- and Rg-infused rats. In contrast, NR2B level is decreased in CA3 in Rgl-infused rats. The level of NR2C mRNA is increased in the granule layer of cerebellum in only Rg1 but not Rc infused rats. These results show that structure difference of ginsenoside may diversely affect the modulation of expression of NMDA receptor subunit mRNA after infusion into cerebroventricle in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1753-1757
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• 2012

A new liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of ginsenoside Rb1 in human plasma was developed and validated. The separation was performed on a Agilent C18 column ($4.6mm{\times}150mm$, particle size 5 ${\mu}m$) with a gradient elution of 0.1% formic acid in water and 0.1% formic acid in methanol and a flow rate of 0.9 mL/min. The analyte was determined using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode (m/z 1131.714${\rightarrow}$365.303). Human plasma samples were extracted with acetone : water (50:50) by the liquid-liquid extraction method. The method was linear over the dynamic range of 10~500 ng/mL with a correlation coefficient of r=0.9995. The intra-and inter-day precision over the concentration range of ginsenoside Rb1 was lower than 5.8% (correlation of variance, CV), and the accuracy was between 96.0~104.6%. This LC-MS/MS assay of ginsenoside Rb1 in human plasma is applicable for quantification in a pharmacokinetic study.