title: Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production.
abstract: BACKGROUND
  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.
  
  
  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 (3)H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-α were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-γ and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-α. 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-γ2, 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-α. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-α and IFN-γ and in LPS-stimulated mouse peritoneal macrophages.
  
  
  CONCLUSIONS
  Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-γ pathway by directly increasing the expressions of PPAR-γ2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-α production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes.
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Min-Fei
authors.initials: MF
authors.lastname: Yang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Su
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Jiang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: You
authors.forename: Yin-Jing
authors.initials: YJ
authors.lastname: Yang
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Zhang
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D052242:Adiponectin; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D036145:Ginsenosides; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D047495:PPAR gamma; C495693:Slc2a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C049864:ginsenoside Re; D005947:Glucose