• Journal of Ginseng Research
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• v.45 no.2
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• pp.334-343
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• 2021

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo. Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P < 0.05). The gut metagenomic analysis also revealed the functional gene enrichment for terpenoid/polyketide metabolism, glycolysis, gluconeogenesis, propanoate metabolism, etc. Conclusion: These findings imply that prebiotics may selectively promote the proliferation of certain bacterial stains with glycoside hydrolysis capacity, thereby, subsequently improving the biotransformation and bioavailability of primary ginsenosides in vivo.

• BMB Reports
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• v.32 no.4
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• pp.339-344
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• 1999

We studied the effects of ginsenosides in immature rats based upon the previous results that ginseng has a suppressive or anticonvulsive activity. To examine the suppressive effect of ginsenosides on kainic acid-induced seizures, the severities and frequencies were observed for 4 h after injection of kainic acid (KA; i.p., 2 mg/kg b.w.) using 10-day-old male Sprague-Dawley rats ($22{\pm}2\;g$). Protopanaxadiol saponins such as ginsenoside-Rb1 (Rb1), ginsenoside-Rb2 (Rb2), ginsenoside-Rc (Rc), and ginsenoside-Rd(Rd) generally reduced the seizure activities while protopanaxatriol saponins such as ginsenoside-Rg1 (Rg1) and ginsenoside-Re (Re) rather increased stereotypic "paddling-like" movements. When vinyl-GABA (v-G) was injected together with Rb1 or Rc, KA-induced seizure severities were additionally reduced only by the injection of Rc, but not by Rb1. The level of gamma isozyme of protein kinase C (PKC-${\gamma}$) in the hippocampus increased about three times as much as that of normal rats at 4 h after KA injection. The increased level of PCK-${\gamma}$ by KA was significantly reduced to about 35% by the coinjection with v-G alone, but it was not changed by v-G together with Rb1 or Rc. The increased level of PKC-${\gamma}$ at 4 h after injection of KA was not consistent with the reduction of seizure severities between Rb1 and Rc. These results suggest that Rc and Rb1 may reduce seizure severity independent of PKC-${\gamma}$ levels, and Rc may additionally act with v-G regarding the GABA metabolism during the stage of KA-induced seizures in the immature rats.

• Journal of Ginseng Research
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• v.23 no.3 s.55
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• pp.164-171
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• 1999

Microwave-assisted extraction, which is known to rapidly extract target compounds from natural products, was monitored by response surface methodology (RSM) while extracting ginsenosides by using microwave extraction system (MES) equipped with closed vessels, and was confirmed on its extraction efficiency. On the whole, coefficients of determinations $(R^2)$ of the models on ginsenoside contents of extracts with various extraction conditions were above 0.83 (p<0.1). $Ginsenoside-Rb_2,\;-Rc,\;-Re\;and\;-Rg_1$ were maximized in $140^{\circ}C$ of extraction temperature and $50\~75\%$ range of ethanol concentration. Unknown compound peak on HPLC chromatogram observed at extraction temperature over $120^{\circ}C$, increased at the extraction temperature of $150^{\circ}C$. The extraction temperature of $ginsenoside-Rb_2$ and -Re increased from $129^{\circ}C\;to\;147^{\circ}C$ with including unknown compound, and $R^2$ of the models on ginsenoside contents of extracts increased with including unknown compound into ginsenoside $Rb_2$ and Re. Contents of unknown compound were minimized in $67.33\%$ of ethanol concentration, $99.34^{\circ}C$ of extraction temperature and 3.65 min of extraction time. Ginsenoside contents extracted by microwave system for 8 min showed a similar tendency to those of the current extraction method for 40 hrs.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.315-322
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• 2019

Seasonal ginsenoside flux in the leaves of 5-year-old Panax ginseng was analyzed from the field-grown ginseng, for the first time, to study possible biosynthesis and translocation of ginsenosides. The concentrations of nine major ginsenosides, Rg1, Re, Rh1, Rg2, R-Rh1, Rb1, Rc, Rb2, and Rd, were determined by UHPLC during the growth in between April and November. It was confirmed total ginsenoside content in the dried ginseng leaves was much higher than the roots by several folds whereas the composition of ginsenosides was different from the roots. The ginsenoside flux was affected by ginseng growth. It quickly increased to 10.99±0.15 (dry wt%) in April and dropped to 6.41±0.14% in May. Then, it slowly increased to 9.71±0.14% in August and maintained until October. Ginsenoside Re was most abundant in the leaf of P. ginseng, followed by Rd and Rg1. Ginsenosides Rf and Ro were not detected from the leaf. When compared to the previously reported root data, ginsenosides in the leaf appeared to be translocated to the root, especially in the early vegetative stage even though the metabolite translocated cannot be specified. The flux of ginsenoside R-Rh1 was similar to the other (20S)-PPT ginsenosides. When the compositional changes of each ginsenoside in the leaf was analyzed, complementary relationship was observed from ginsenoside Rg1 and Re, as well as from ginsenoside Rd and Rb1+Rc. Accordingly, ginsenoside Re in the leaf was proposed to be synthesized from ginsenoside Rg1. Similarly, ginsenosides Rb1 and Rc were proposed to be synthesized from Rd.

• Journal of Ginseng Research
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• v.32 no.4
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• pp.390-396
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• 2008

For evaluating the quality of ginseng, simple and fast analysis methods are needed to determine the ginsenoside content of the ginseng products. The aim of this study was therefore to optimize conditions for fast analysis of the ginsenosides, the active ingredients in extracts of Korean red ginseng. When tandem HPLC mass spectrometry (HPLC-MS/MS) was used, four forms of ginsenoside, Rb1, Rb2, Rc, and Re, were readily separated in seven minutes using a gradient mobile phase (acetonitrile and water containing acetic acid). This is the shortest separation time reported among the studies of major ginsenoside analysis. When gradient HPLC with UV detection was used, the detection limit was high, but separation of these four ginsenosides required 25 minutes using acetonitrile and water containing formic acid as a mobile phase. HPLC-MS/MS was able to separate ginsenoside Rg1 easily regardless of the mobile phase condition, but the HPLC-UV could not separate Rg1 because acetonitrile concentration in the mobile phase had to be maintained below 20%. Ginsenoside peaks were clearer and had more sensitive detection limits when Korean red ginseng extract was analyzed by the HPLC-MS/MS, but the UV detection was useful for chromatographic fingerprinting of all four major ginsenosides of the extract: Rb1, Rb2, Rc, and Re. Extracts were found to contain 2.17 mg, 1.51 mg, 1.29 mg, and 0.46 mg of ginsenoside Rb1, Rb2, Rc, Re, respectively, per gram weight. The ratios of each ginsenoside in the extracts were 1.0 : 0.7 : 0.6 : 0.2, respectively. Taken together, the results indicate that HPLC-MS/MS spectrometry could be the most useful method for rapid analysis of even small amounts of major ginsenosides, while HPLC with UV detection could also be used for rapid analysis of major ginsenosides and for quality control of ginseng products.

• Korean Journal of Biological Psychiatry
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• v.12 no.1
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• pp.42-61
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• 2005

Objectives:The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. Methods:SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1($80{\mu}M$, $40{\mu}M$, $20{\mu}M$). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. Results:Treatment of SH-SY5Y cells with $80{\mu}M$ ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(${\geq}$3 fold) in Rg1 treated cells and 40 genes were up-regulated(${\geq}$2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1-group. Conclusion:Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

• BMB Reports
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• v.42 no.4
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• pp.194-199
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• 2009

The effects of the ginsenoside Rb2 (Rb2) on lipid metabolism were characterized in 3T3-L1 adipocytes to evaluate their utility for treating obesity. While the amounts of total cholesterol and triacylglycerol (TAG) were markedly increased in the adipocytes treated with high amounts of cholesterol and fetal bovine serum (FBS), the test groups treated with Rb2 showed levels that were close to normal. The effect of Rb2 on these cells was comparable to that of lovastatin. Rb2 enhanced the expression of the sterol regulated element binding protein (SREBP) mRNA whereas treatment with cholesterol and FBS led to a reduction in the abundance of this transcript. The activity of fatty acid synthetase (FAS) was lower in the cholesterol group compared to the Rb2 treatment group suggesting that the observed decrease in cholesterol levels and activated SREBP was mediated by Rb2. Treatment with Rb2 also resulted in a decrease in TAG levels in adipocytes cultured under high fatty acid conditions. This effect was mediated by stimulating the expression of SREBP and Leptin mRNA, suggesting that Rb2 might be a valuable component capable of lowering the levels of lipids.

• Natural Product Sciences
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• v.20 no.2
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• pp.119-125
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• 2014

According to the results of my study on the chromatographic analysis of fresh ginseng (Panax ginseng C. A. Meyer) roots, most of the contents of protopanxadiol ginsenosides $Rb_1$, Rc, $Rb_2$, and Rd are derived from the corresponding malonyl ginsenosides in fresh ginseng by a heat process. Also, I confirmed that acetyl ginsenosides are naturally occurring constituents in fresh ginseng, not decarboxylates from malonyl ginsenosides. Seven neutral ginsenosides $Rg_1$, Re, Rf, Rc, $Rb_1$, $Rb_2$, and Rd were transformed to specific conversions in red ginseng preparation conditions. The conversion paths progress by three rules concluded from my study. These conversion rules are I: the ether bond is stable at positions 3 and 6 in the dammarane skeleton, II: the ether bond between sugars is stable in glycosides, and III: the ether bond to glycosides is unstable at position 20 in the dammarane skeleton.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.75-80
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• 2018

Background: The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells. Methods: LLC-PK1 cells were treated with FK506 and ginsenosides, and cell viability was measured. Protein expressions of mitogen-activated protein kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by Western blotting analyses. The number of apoptotic cells was measured using an image-based cytometric assay. Results: Reduction in cell viability by $60{\mu}M$ FK506 was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with ginsenoside Rb1. The number of apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 ($10{\mu}M$ and $50{\mu}M$). Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506-induced apoptosis were mediated by the inhibition of mitogen-activated protein kinases and caspase activation.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.2
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• pp.418-424
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• 2009

The analytical conditions of ginsenosides were optimized using high performance liquid chromatography (HPLC). The optimal analysis conditions were set up from the experiments using different gradient conditions, and the ginsenosides contents of red ginseng products and their raw materials were analysed. Red ginseng contained 0.29% Rg1, 0.82% Rb1, 0.38% Rc, 0.32% Rb2, 0.11% Rd, showing the highest ginsenoside contents. Among the red ginseng products, red ginseng extract showed the highest content. The ginsenoside contents were varied according to the raw material type and product type. Re and Rb1 contents were the highest in most raw materials and products.