Objectives : Cyclooxygenase (COX) plays a central role in the inflammatory cascade by converting arachidonic acid into prostaglandin. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, it is responsible for propagating the inflammatory response and thus, considered as the best target for anti-inflammatory drugs. The present study investigated the modulatory effect of ginsenoside Rg3, a principle active ingredient in Panax ginseng, on COX-2 expression in the brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Methods : Because systemic LPS treatment induces COX-2 expression immediately in the brain, ginsenoside Rg3 was treated orally with doses of 10, 20, and 30 mg/kg at 1 hour before the LPS (3 mg/kg, i.p.) injection. At 4 hours after the LPS injection, COX-2 mRNA was measured by real-time polymerase chain reaction method, COX-2 protein levels were measured by Western blotting. In addition, COX-2 expressions in brain tissue were observed with immunohistochemistry and double immunofluoresence labeling. Results : Ginsenoside Rg3 (20 and 30 mg/kg) significantly attenuates up-regulation of COX-2 mRNA and protein expression in brain tissue at 4 hours after the LPS injection. Moreover, ginsenoside Rg3 (20 mg/kg) significantly reduced the number of COX-2 positive neurons in the cerebral cortex and amygdala. Conclusion : These results indicate that ginsenoside Rg3 plays a modulatory role in neuroinflammation through the inhibition of COX-2 expression in the brain and suggest that ginsenoside Rg3 and ginseng may be effective on neurodegenerative diseases caused by neuroinflammation.
Ha, Kang-Su;Kim, Ki-Hwan;Lim, Hyo-Jeong;Ki, Young-Jae;Koh, Young-Youp;Lim, Dong-Yoon
Natural Product Sciences
/
v.27
no.2
/
pp.86-98
/
2021
This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K+, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and Nω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na+ and Ca2+ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca2+ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT1-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.
The purpose of this study is to develop a new preparation process of ginseng extracts having high concentrations of ginsenoside $Rg_3$, $Rg_5$ and $Rk_1$, a special component of Red ginseng. Chemical transformation from ginseng saponin glycosides to prosapogenin was analyzed by the HPLC. Extracts of White ginseng (Panax ginseng) and Fine White ginseng were processed under several treatment conditions including microwave and vinegar (about 14% acidity) treatments. Results of those treatments showed that the quantity of ginsenoside $Rg_3$ increased by over 0.6% at 4 minutes of pH 2~4 vinegar and microwave treatments. The results of processing with MWG-4 indicate that the Microwave and vinegar processed white ginseng extracts (about 14% acidity) that had gone through 4-minute treatments were found to contain the largest amount of ginsenoside $Rg_3$ (0.626%), $Rg_5$ (0.514%) and $Rk_1$ (0.220%). Results of treatments with MFWG-5 showed that the Fine White ginseng extracts that had been processed with microwave and vinegar (about 14% acidity) for 5 minutes were found to contain the largest amount of ginsenoside $Rg_3$ (4.484%), $Rg_5$ (3.192%) and $Rk_1$ (1.684%). It is thought that such results provide basic information in preparing White ginseng and Fine White ginseng extracts with functionality enhanced.
Background: Red ginseng (RG) extract, especially ginsenoside Rg1 and Rb1 fractions has been reported to have antithrombotic activities. However, gastric instability and low intestinal permeability are considered to be obstacles to its oral administration. We hypothesized that stability, permeability, and activities of RG might be improved by encapsulation within nanoparticles (NPs) prepared with antithrombotic coating materials. Methods: RG-loaded chitosan (CS) NPs (PF-NPs) were prepared by complex ionic gelation with the antithrombotic wall materials, polyglutamic acid (PGA), and fucoidan (Fu). The concentrations of PGA (mg/mL, X1) and Fu (mg/mL, X2) were optimized for the smallest particle size by response surface methodology. Antithrombotic activities of RG and PF-NPs were analyzed using ex vivo and in vivo antiplatelet activities, in vivo carrageenan-induced mouse tail, and arteriovenous shunt rat thrombosis models. Results: In accordance with a quadratic regression model, the smallest PF-NPs (286 ± 36.6 nm) were fabricated at 0.628 mg/mL PGA and 0.081 mg/mL Fu. The inhibitory activities of RG on ex vivo and in vivo platelet aggregation and thrombosis in in vivo arteriovenous shunt significantly (p < 0.05) increased to approximately 66.82%, 35.42%, and 38.95%, respectively, by encapsulation within PF-NPs. For an in vivo carrageenan-induced mouse tail thrombosis model, though RG had a weaker inhibitory effect, PF-NPs reduced thrombus significantly due to the presence of PGA and Fu. Conclusion: PF-NPs contributed to improve the activities of RG not only by nanoencapsulation but also by antithrombotic coating materials. Therefore, PG-NPs can be suggested as an efficient delivery system for oral administration of RG.
Chenyang Ran;Meili Lu;Fang Zhao;Yi Hao;Xinyu Guo;Yunhan Li;Yuhong Su;Hongxin Wang
Journal of Ginseng Research
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v.48
no.4
/
pp.405-416
/
2024
Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH. Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels. Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs. Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway.
Kim, Yunjeong;Han, Song-Hee;Jeon, Ji-Young;Hwang, Min-Ho;Im, Yong-Jin;Lee, Sun Young;Chae, Soo-Wan;Kim, Min-Gul
Analytical Science and Technology
/
v.26
no.4
/
pp.221-227
/
2013
A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the investigation of the ginsenoside Rg1 in human plasma. After addition of internal standard (digoxin), plasma was diluted with acetone and methanol (80:20), the supernatant was concentrated and analyzed by LC-MS/MS. The optimal chromatographic separation was achieved on an Agilent Eclipse XDB-C18 column ($4.6{\times}150mm$, $5{\mu}m$) with a mobile phase of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.9 mL/min gradient mode. The standard calibration curve for ginsenoside Rg1 was linear ($r^2=0.9995$) over the concentration range 1~500 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of ginsenoside Rg1 was lower than 7.53% (correlation of variance, CV), and accuracy exceeded 98.28%. This LC-MS/MS assay of ginsenoside Rg1 in human plasma is applicable for quantifying in the pharmacokinetic study.
Oh, Seong-Hwa;Choi, Soo-Yeon;Lee, Nu Rim;Lee, Jung No;Kim, Dong-Seok;Lee, Sang-Hwa;Park, Sung-Min
Journal of the Society of Cosmetic Scientists of Korea
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v.40
no.3
/
pp.297-305
/
2014
Red ginseng (RG) contains specific ginsenosides (Rg2, Rg3) which show various pharmacological effects and absorption rate in the body better than panax ginseng. Therefore many people have been used it for health for a long time. Furthermore, many researchers have been studying its biological activities for a long times because fermentation generates lots of beneficial small molecules good for health. In this study, we fermented red ginseng with mycelium of Leatiporus sulphures var. miniatus for 7 days. As a result, we found that three ginsenosides Rg1, Re and Rb2 were decreased from 0.24, 0.25, 0.16 mg/g to 0.12, 0.1, 0.03 mg/g respectively HPLC analysis. In addition, we studied biological activities of fermented red ginseng (FRG) about skin ageing such as anti-inflammation, cell migration, anti-oxidation, collagen type 1 synthesis, and MMP-1 inhibition activities. As a result, FRG were shown higher anti-inflammatory and cell migration promoting activities than RG. FRG inhibited production of nitric oxide (NO) and mRNA expression of inducible nitric oxide synthase (iNOS) and decreased interleukin (IL)-6 induced by LPS stimulation in RAW 264.7 cells. In conclusion, this study suggest that FRG could be a potential source as a new natural anti-inflammatory agent.
Kim, Na-Mi;Lee, Seong-Kye;Cho, Hae-Hyun;So, Seung-Ho;Jang, Dong-Pil;Han, Sung-Tai;Lee, Jong-Soo
Journal of Ginseng Research
/
v.33
no.3
/
pp.183-188
/
2009
To produce ginsenoside-Rg$_3$ enriched edible yeast, ginseng steaming effluent (GSE) was used for yeast cultivation in this study. Four kinds of edible yeasts were cultured in sterilized GSE (2% w/v, pH 6.5), without any nutrient, for 48 h at 30$^{\circ}C$, and their growth and ginsenoside compositions were determined. Among the yeasts, Saccharomyces cerevisiae showed the highest growth in the GSE medium. 267.1 mg of Saccharomyces cerevisiae biomass was produced from 1 g of GSE solid and ginsenoside-Rg$_3$ contents was determined with 0.033 mg. Saccharomyces cerevisiae also showed the best overall acceptability, with a herbal and fermentative flavor and a slightly bitter taste. From these data, we conclude that Saccharomyces cerevisiae is the excellent strain for production of ginsenoside-Rg$_3$ enriched edible yeast using GSE.
Objective; Antistress effect of Korean red ginseng (RG) on postmenopausal women with severe climacteric syndrome (CS) were evaluated from the viewpoint of traditional KAMPO-medicine and Western medicine. Methods; All patients with CS were treated with daily oral administration of 6g RG for 30 days. Nine patients with CS were evaluated with the use of diagnostic scores for KI-deficiency (deficiency of vital energy) and OKETSU (blood stagnation) syndrome from the viewpoint of KAMPO-medicine. In the same patients with CS, peripheral blood levels of ${\beta}$-endorphin and total plasminogen activator inhibitor-1 (t-PAI-1) were measured before and after treatment with RG. In another group, 12 patients with CS, psychological test using CMI, STAI and SDS were performed from the viewpoint of Western medicine. Stress related hormones, such as ACTH, cortisol and DHEA-S in those 12 patients with CS were also measured before and after treatment with RG. Results; KI-deficiency score and OKETSU score in patients with CS were significantly (p<0.001) higher than those in patients without CS. After treatment with RG, both scores were markedly (p<0.001) decreased compared to before treatment with RG. ${\beta}$-endorphin levels in patients with CS were significantly (p<0.05) higher than those in patients without CS. Total PAI-levels in patients with CS were increased before treatment with RG. No significant difference, however, were observed between patients with and without CS. After treatment with RG, both levels of ${\beta}$-endorphin and total PAI-1 in patients with CS were significantly (p<0.001 and p<0.05, respectively) decreased compared to before treatment with RG. CMI and STAI scores in patients with CS were significantly (p<0.05) higher than those in patients without CS. SDS scores in patients with CS were also markedly (p<0.00l) higher than in those without CS. After treatment with RG, all scores decreased within normal range. DHEA-S levels in patients with CS were about a half of those without CS. Consequently, cortisol/DHEA-S (C/D) ratio was significantly(p<0.001) higher in patients with CS than in those without CS. Although the decreased DHEA-S levels were not restored to the levels in patients without CS, the C/D ratio decreased significantly (p<0.05) after treatment with RG. Conclusion; Reinforcement of vital energy and improvement of stagnant blood circulations by oral administration of RG were elucidated from the viewpoint of traditional KAMPO-medicine. From the viewpoint of Western medicine, effect of RG on postmenopsusal women with CS seemed to be brought about in part by not only an improvement of psychoneuroendocrine dysfunctions but also an amelioration of blood coagulation systems.
Objective; Antistress effect of Korean red ginseng (RG) on postmenopausal women with severe climacteric syndrome (CS) were evaluated from the viewpoint of traditional KAMPO-medicine and Western medicine. Methods; All patients with CS were treated with daily oral administration of 6g RG for 30 days. Nine patients with CS were evaluated with the use of diagnostic scores for KI-deficiency (deficiency of vital energy) and OKETSU (blood stagnation) syndrome from the viewpoint of KAMPa-medicine. In the same patients with CS, peripheral blood levels of $\beta$-endorphin and total plasminogen activator inhibitor-1 (t-PAI-1) were measured before and after treatment with RG. In another group, 12 patients with CS, psychological test using CMI, STAI and SDS were performed from the viewpoint of Western medicine. Stress related hormones, such as ACTH, cortisol and DHEA-S in those 12 patients with CS were also measured before and after treatment with RG. Results; KI-deficiency score and OKETSU score in patients with CS were significantly (p<0.001) higher than those in patients without CS. After treatment with RG, both scores were markedly (p<0.001) decreased compared to before treatment with RG. ${\beta}-endorphin$ levels in patients with CS were significantly (p<0.05) higher than those in patients without CS. Total PAI-I levels in patients with CS were increased before treatment with RG. No significant difference, however, were observed between patients with and without CS. After treatment with RG, both levels of ${\beta}-endorphin$ and total PAI-l in patients with CS were significantly (p<0.01 and p<0.05, respectively) decreased compared to before treatment with RG. CMI and STAI scores in patients with CS were significantly (p<0.05) higher than those in patients without CS. SDS scores in patients with CS were also markedly (p<0.001) higher than in those without CS. After treatment with RG, all scores decreased within normal range. DHEA-S levels in patients with CS were about a half of those without CS. Consequently, cortisol/DHEA-S (C/D) ratio was significantly (p<0.001) higher in patients with CS than in those without CS. Although the decreased DHEA-S levels were not restored to the levels in patients without CS, the C/D ratio decreased significantly (p<0.05) after treatment with RG. Conclusion; Reinforcement of vital energy and improvement of stagnant blood circulations by oral administration of RG were elucidated from the viewpoint of traditional KAMPO-medicine. From the viewpoint of Western medicine, effect of RG on postmenopausal women with CS seemed to be brought about in part by not only an improvement of psychoneuroendocrine dysfunctions but also an amelioration of blood coagulation systems.
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