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Ginsenoside Re reduces insulin resistance through activation of PPAR-gamma pathway and inhibition of TNF-alpha production

Authors Gao, Yang; Yang, Min-fei; Su, Ya-ping; Jiang, Hui-min; You, Xiao-juan; Yang, Yin-jing; Zhang, Hai-long

Journal JOURNAL OF ETHNOPHARMACOLOGY , MAY 20 2013,2:147

DOI 10.1016/j.jep.2013.03.057 PubMed 23545455

Abstract Ethnopharmacological relevance: Panax ginseng is a well-known traditional Chinese medicine and has been used for treatment of various diseases for more than four thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents are reported to possess antidiabetic activity, but their antihyperglycemic mechanisms are not fully elucidated. In the present study, the mechanisms of action of ginsenoside Re were investigated in vitro models.Materials and methods: 3T3-L1 cells were chosen as the model to investigate the molecular mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by insulin in the absence or presence of ginsenoside Re were quantified by measuring H-3-2-deoxy-D-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-alpha were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-gamma and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-alpha. And western blot analysis was performed to determine the translocation of GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes and in macrophages were investigated through measurement of nitrite concentration by Griess reagent.Results: Ginsenoside Re induced adipogenesis of 3T3-L1 adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR-gamma 2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also increased production and release of adiponectin. Although having no effects on GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the membranes. In addition, Re inhibited the expression and release of TNF-alpha. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-alpha and IFN-gamma and in LPS-stimulated mouse peritoneal macrophages.Conclusions: Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-gamma pathway by directly increasing the expressions of PPAR-gamma 2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-alpha production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Species covered 人参 Panax ginseng