• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1109-1114
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• 2008

To understand the role of intestinal microflora in the biological effect of functional herbs, which have been used in Korea, Japan, and China as traditional medicines, and suggest new bioactive compounds transformed from herbal constituents, the metabolic activities of the functional herb components (ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, poncirin, hesperidin, glycyrrhizin, and baicalin) toward their bioactive compounds (compound K, crocetin, benzaldehyde, genipin, daidzein, ginsenoside Rh1, ponciretin, hesperetin, 18b-glycyrrhetic acid, and baicalein) were measured in fecal specimens. The metabolic activities of these components were $882.7{\pm}814.5$, $3,938.1{\pm}2,700.8$, $2,375.5{\pm}913.7$, $1,179.4{\pm}795.7$, $24.6{\pm}10.5$, $11.4{\pm}10.8$, $578.8{\pm}206.1$, $1,150.0{\pm}266.1$, $47.3{\pm}58.6$, and $12,253.0{\pm}6,527.6\;{\mu}mol/h/g$, respectively. No differences were found in the metabolic activities of the tested components between males and females, although these metabolic activities between individuals are extensively different. The metabolites of functional herb components showed more potent cytotoxicity against tumor cells than nonmetabolites. These findings suggest that intestinal microflora may activate the pharmacological effect of herbal food and medicines and must be the biocatalytic converter for the transformation of herbal components to bioactive compounds.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.103-111
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• 2024

Background: Ginseng (Panax ginseng Mayer) is an important natural medicine. However, a long culture period and challenging quality control requirements limit its further use. Although artificial cultivation can yield a sustainable medicinal supply, research on the association between the transplantation and chaining of metabolic networks, especially the regulation of ginsenoside biosynthetic pathways, is limited. Methods: Herein, we performed Liquid chromatography tandem mass spectrometry based metabolomic measurements to evaluate ginsenoside accumulation and categorise differentially abundant metabolites (DAMs). Transcriptome measurements using an Illumina Platform were then conducted to probe the landscape of genetic alterations in ginseng at various ages in transplantation mode. Using pathway data and crosstalk DAMs obtained by MapMan, we constructed a metabolic profile of transplantation Ginseng. Results: Accumulation of active ingredients was not obvious during the first 4 years (in the field), but following transplantation, the ginsenoside content increased significantly from 6-8 years (in the wild). Glycerolipid metabolism and Glycerophospholipid metabolism were the most significant metabolic pathways, as Lipids and lipid-like molecule affected the yield of ginsenosides. Starch and sucrose were the most active metabolic pathways during transplantation Ginseng growth. Conclusion: This study expands our understanding of metabolic network features and the accumulation of specific compounds during different growth stages of this perennial herbaceous plant when growing in transplantation mode. The findings provide a basis for selecting the optimal transplanting time.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.171-180
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• 2024

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. Results: HUVEC was the more sensitive cell line to the anti-proliferative effects of S-Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S-Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. Conclusion: The combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.

• 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.36 no.1
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• pp.1-15
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• 2012

The major commercial ginsengs are Panax ginseng Meyer (Korean ginseng), P. quinquifolium L. (American ginseng), and P. notoginseng (Burk.) FH Chen (Notoginseng). P. ginseng is the most commonly used as an adaptogenic agent and has been shown to enhance physical performance, promote vitality, increase resistance to stress and aging, and have immunomodulatory activity. These ginsengs contain saponins, which can be classified as dammarane-type, ocotillol-type and oleanane-type oligoglycosides, and polysaccharides as main constituents. Dammarane ginsenosides are transformed into compounds such as the ginsenosides $Rg_3$, $Rg_5$, and $Rk_1$ by steaming and heating and are metabolized into metabolites such as compound K, ginsenoside $Rh_1$, proto- and panaxatriol by intestinal microflora. These metabolites are nonpolar, pharmacologically active and easily absorbed from the gastrointestinal tract. However, the activities metabolizing these constituents into bioactive compounds differ significantly among individuals because all individuals possess characteristic indigenous strains of intestinal bacteria. To overcome this difference, ginsengs fermented with enzymes or microbes have been developed.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.270-277
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• 2014

Background: The effect of methyl jasmonate (MJ) on ginsenoside production in different organs of ginseng (Panax ginseng Meyer) was evaluated after the whole plant was dipped in an MJ-containing solution. MJ can induce the production of antioxidant defense genes and secondary metabolites in plants. In ginseng, MJ treatment in adventitious root resulted in the increase of dammarenediol synthase expression but a decrease of cycloartenol synthase expression, thereby enhancing ginsenoside biosynthesis. Although a previous study focused on the application of MJ to affect ginsenoside production in adventitious roots, we conducted our research on entire plants by evaluating the effect of exogenous MJ on ginsenoside production with the aim of obtaining new approaches to study ginsenoside biosynthesis response to MJ in vivo. Methods: Different parts of MJ-treated ginseng plants were analyzed for ginsenoside contents (fine root, root body, epidermis, rhizome, stem, and leaf) by high-performance liquid chromatography. Results: The total ginsenoside content of the ginseng root significantly increased after 2 d of MJ treatment compared with the control not subjected to MJ. Our results revealed that MJ treatment enhances ginsenoside production not in the epidermis but in the stele of the ginseng root, implying transportation of ginsenosides from the root vasculature to the epidermis. Application of MJ enhanced protopanaxadiol (PPD)-type ginsenosides, whereas chilling treatment induced protopanaxatriol (PPT)-type ginsenosides. Conclusion: These findings indicate that the production of PPD-type and PPT-type ginsenosides is differently affected by abiotic and biotic stresses in the ginseng plant, and they might play different defense mechanism roles.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.255-265
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• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.636-640
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• 2007

In order to investigate the major metabolite patterns of aged Panax ginseng C.A. Meyer roots, the ginsenoside contents for white ginseng roots of various ages were compared. The 1-year to 6-year old roots were extracted with methanol, and then the methanol-soluble metabolites were analyzed by high performance liquid chromatography (HPLC). The metabolite contents of the 1-year and 2-year roots, including the ginsenosides and minor components, were not different, but the $Rg_1$, Re, and Rc ginsenoside contents between the 2-year and 3-year roots showed significant differences. $Rg_1$ and Rc increased significantly in the 1-year to 2-year roots, and Re increased significantly from the 3-year root age. Rd increased slightly until the 2-year age and decreased from the 3-year age. Based on the ginsenoside distributions and contents at various root ages, we have suggested 2 biogenesis schemes using the ginsenosides that have been isolated from the roots of P. ginseng so far.

• Journal of Ginseng Research
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• v.40 no.1
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• pp.9-17
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• 2016

Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results: The impaired cognitive function and increased hippocampal $A{\beta}$ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.