• Journal of Ginseng Research
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• 제45권6호
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• pp.695-705
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• 2021

Background: Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods: We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results: We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion: Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

• Journal of Ginseng Research
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• 제45권6호
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• pp.683-694
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• 2021

Background: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca²⁺]_i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca²⁺]_i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-b1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl₃ could not further increase the [Ca²⁺]_i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca²⁺]_i and CaN signaling but had no effect on CaSR expression. Conclusion: The activation of CaN pathway and the increase of [Ca²⁺]_i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• 동의생리병리학회지
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• 제18권4호
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• pp.1140-1146
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• 2004

This study was carried out to investigate the comparison of immunomodualtory effects of water-extracted Ginseng Radix(GR), Pilose Asia-bell(PA), Astragali Radix(AR), Astractylodes Rhizoma alba(AA) and Dioscoreae Rhizoma (DR). The parameter examined to assess apparent immunomodulatory effect of the water-extracted GR, PA, AR, AA and DR included the regulation of Nitric oxide (NO), the expression of Th1/Th2 type cytokine, the change of B cell phenotype. The water-extracted GR, PA, AR, AA and DR inhibited NO production and iNOS protein expression in LPS stimulated RAW 264.7 macrophage cells. In the Th1 and Th2 cytokine expression, the water-extracted GR, PA, AR, AA and DR induced IL-2 and IFNr mRNA gene expression. Therefore, it seems that the water-extracted GR, PA, AR, AA and DR have a inducing effect of Th1 type cytokines. In the Flow cytometry analysis, the water-extracted GR, PA, AR, AA and DR did not change B cell phenotype (CD45R/B220). The water-extracted GR, PA, AR, AA and DR have a reducing effect of immune suppression cause by Methotrexate (MTX), an agent of immune suppression. These results suggest that the immunomodulatory effects of the water-extracted GR, PA, AR, AA and DR may be, in part, associated with the inducing IL-2 and IFNr mRNA gene expression in and regulation of NO production in macrophage cells.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2008년도 추계학술발표회
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• pp.470-470
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• 2008

• Journal of Ginseng Research
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• 제35권3호
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• pp.375-383
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• 2011

In the previous report, we have demonstrated that ginsenoside Rc, one of major ginsenosides, is a major component for the restoration for normal growth of worms in cholesterol-deprived medium. In the present study, we further investigated the roles of minor ginsenosides, such as ginsenoside $Rh_1$ and $Rh_2$, ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) and ginsenoside epimers such as 20(R)- and 20(S)-ginsenoside $Rg_3$ in cholesterol-deprived medium. We found that ginsenoside $Rh_1$ almost restored normal growth of worms in cholesterol-deprived medium in F1 generation. However, supplement of ginsenoside $Rh_2$ caused a suppression of worm growths in cholesterol-deprived medium. In addition, CK and PPD also slightly restored normal growth of worms in cholesterol-deprived medium but PPT not. In experiments using ginsenoside epimers, supplement of 20(S)- but not 20(R)-ginsenoside $Rg_3$ in cholesterol-deprived medium also almost restored worm growth. These results indicate that the absence or presence of carbohydrate component at backbone of ginsenoside, the number of carbohydrate attached at carbon-3, and the position of hydroxyl group at carbon-20 of ginsenoside might plays important roles in restoration of worm growth in cholesterol-deprived medium.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.113-118
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• 2012

Ginsenosides are low molecular weight glycosides found in ginseng that exhibit neuroprotective effects through inhibition of $N$-methyl-D-aspartic acid (NMDA) receptor channel activity. Ginsenosides, like other natural compounds, are metabolized by gastric juices and intestinal microorganisms to produce ginsenoside metabolites. However, little is known about how ginsenoside metabolites regulate NMDA receptor channel activity. In the present study, we investigated the effects of ginsenoside metabolites, such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT), on oocytes that heterologously express the rat NMDA receptor. NMDA receptor-mediated ion current ($I_{NMDA}$) was measured using the 2-electrode voltage clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, PPT, but not CK or PPD, reversibly inhibited $I_{NMDA}$ in a concentration-dependent manner. The $IC_{50}$ for PPT on $I_{NMDA}$ was $48.1{\pm}4.6\;{\mu}M$, was non-competitive with NMDA, and was independent of the membrane holding potential. These results demonstrate the possibility that PPT interacts with the NMDA receptor, although not at the NMDA binding site, and that the inhibitory effects of PPT on $I_{NMDA}$ could be related to ginseng-mediated neuroprotection.

• Journal of Ginseng Research
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• 제44권6호
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• pp.784-789
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• 2020

Background: The separation of isomeric compounds from a mixture is a recurring problem in chemistry and phytochemistry research. The purification of pharmacologically active ginsenoside Rb₃ from ginseng extracts is limited by the co-existence of its isomer Rb₂. The aim of the present study was to develop an enzymatic elimination-combined purification method to obtain pure Rb₃ from a mixture of isomers. Methods: To isolate Rb₃ from the isomeric mixture, a simple enzymatic selective elimination method was used. A ginsenoside-transforming glycoside hydrolase (Bgp2) was employed to selectively hydrolyze Rb₂ into ginsenoside Rd. Ginsenoside Rb₃ was then efficiently separated from the mixture using a traditional chromatographic method. Results: Chromatographic purification of Rb₃ was achieved using this novel enzymatic elimination-combined method, with 58.6-times higher yield and 13.1% less time than those of the traditional chromatographic method, with a lower minimum column length for purification. The novelty of this study was the use of a recombinant glycosidase for the selective elimination of the isomer. The isolated ginsenoside Rb₃ can be used in further pharmaceutical studies. Conclusions: Herein, we demonstrated a novel enzymatic elimination-combined purification method for the chromatographic purification of ginsenoside Rb₃. This method can also be applied to purify other isomeric glycoconjugates in mixtures.

• 약학회지
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• 제34권5호
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• pp.365-373
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• 1990

The effects of the protein fraction of Panax ginseng on primary cultured chicken embryonic brain cells and DRG cultured with a deficient medium were studied. The protein fraction was further fractionated into four groups according to the molecular weight; larger than 10,000 dalton(fraction A), between 5,000 and 10,000 daltons(fraction B), between 1,000 and 5,000 daltons(fraction C), between 500 and 1,000 daltons(fraction D). All four protein fractions at the concentration of $100\;{\mu}g/ml$ significantly increased the number of the brain cells which promoted the neurite outgrowth. The activity of PDHC in the brain cells was elevated significantly by the protein fraction B at the concentration of $100\;{\mu}g/ml$. It was noted that $100\;{\mu}g/ml$ protein fraction C and D significantly enhanced the synthesis of protein in the brain cells. At the concentration of $100\;{\mu}g/ml$, the protein fraction B enhanced RNA synthesis and the protein fraction A significantly enhanced DNA synthesis in the brain cells. The protein fractions B, C, and D significantly promoted the neurite outgrowth of DRG at the concentration of $100\;{\mu}g/ml$.

• 한국약용작물학회지
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• 제21권3호
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• pp.184-190
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• 2013

This study was carried out to investigate ginsenoside content in different root parts and the correlation between root diameter and ginsenoside composition of Panax ginseng C. A. Meyer cultivated by direct seeding. The unit contents of ginsenoside were 29.65, 28.76, 26.34 mg/g, respectively in 4, 5, 6 years old. However, the total contents of ginsenoside were 431.97, 606.56, 657.80 mg/root, respectively. Total ginsenoside content of fine root was higher than that of main root and lateral root. These tendencies were related to decrease by the increase of root diameter. When diameter of main root and lateral root were the same in different ages, the total ginsenoside content was higher in the order of 4 > 5 > 6 years old roots. Except for ginsenoside-Rg1, other ginsenosides components (PD/PT and total ginsenosides) had highly negative correlation with the root diameter within whole root, main root, lateral root and fine root, which indicated that ginsenoside content is correlated to root diameter. As results, it is suggested that ginsenoside content can be predicted.