title: Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats.
abstract: OBJECTIVE
  To explore the mechanism of action of gypenosides (GPs) on type 2 diabetes mellitus and non-alcoholic fatty liver disease (T2DM-NAFLD) in rats.
  
  
  METHODS
  Sixty rats were randomly divided into a healthy group, an untreated disease model group and GP-treatment groups. The study involved the evaluation of biochemical parameters, including serum aspartate transaminase (AST), alanine transferase (ALT), blood glucose (BG), triglycerides (TG) and total cholesterol (TC). Additionally, the protective effect of the treatments were confirmed histopathologically and the expression of TNF-α and NF-κB in the rat liver was analyzed using immunohistochemistry. The expression of proliferator-activated receptor gamma (PPARγ) and cytochrome P450 (CYP450) 1A1 mRNA was determined by quantitative RT-PCR.
  
  
  RESULTS
  GP treatments at oral doses of 200, 400, and 800 mg/kg per day significantly decreased the levels of serum AST and ALT (P<0.05, P<0.01), especially at the dose of 800 mg/kg per day. To a similar extent, GP at 800 mg/kg per day reduced the levels of BG (4.19±0.47, P<0.01), TG (80.08±10.05, P<0.01), TC (134.38±16.39, P<0.01) and serum insulin (42.01±5.04, P<0.01). The expression of TNF-α and NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner, and the expression of PPARγ and CYP4501A1 mRNA, as measured using quantitative real-time PCR, were significantly down-regulated by GPs. Moreover, GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dose-dependent manner.
  
  
  CONCLUSIONS
  This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-α and NF-κB proteins, and PPARγ and CYP4501A1 mRNAs.
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Jin-Ke
authors.initials: JK
authors.lastname: Li
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Ru-Gui
authors.initials: RG
authors.lastname: Li
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhan
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Du
authors.affiliation: Qin He, Jin-Ke Li, Fang Li, Ru-Gui Li, Guo-Qing Zhan, Gang Li, Wei-Xing Du, Hua-Bing Tan, Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Tan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D029774:Gynostemma; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D016328:NF-kappa B; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C474918:gypenoside; D019363:Cytochrome P-450 CYP1A1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Cytochrome P4501A1; Gypenosides; Non-alcoholic fatty liver; PPARγ; Type 2 diabetes mellitus