title: Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway.
abstract: OBJECTIVE
  Liver fibrosis is a reversible wound-healing response that occurs following liver injury. In this study, we aimed to investigate the possible protective effects of ursolic acid in liver fibrosis induced by carbon tetrachloride (CCl4).
  
  
  METHODS
  ICR mice were randomly divided into six groups (Group 1: normal; Group 2: CCl4-treated group; Group 3: CCl4 plus ursolic acid 25mg/kg group; Group 4: CCl4 plus ursolic acid 50mg/kg group; Group 5: CCl4 plus colchicine 1mg/kg group; Group 6: ursolic acid 50mg/kg group). Mice were administered with CCl4 (2 mL of CCl4 in olive oil (1:1, v/v) per kg body weight twice weekly) by intraperitoneal injection and oral injection of colchicine (1mg/kg) or ursolic acid (25, 50mg/kg) daily. After six weeks, serum aminotransferase activity, hepatic reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS), antioxidase (SOD, CAT, GPx) activity and histopathological analysis were performed. The levels of nuclear factor E2-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase-1 (NQO1), glutathione S-transferase (GST) and heme oxygenase-1 (HO-1), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS), Bcl-2 and caspase-3 were measured.
  
  
  RESULTS
  Ursolic acid significantly prevented CCl4-induced hepatotoxicity and fibrosis, indicated by both diagnostic indicators and histopathological analysis. CCl4-induced profound elevations of oxidative stress, inflammation and apoptosis in liver were suppressed by ursolic acid.
  
  
  CONCLUSIONS
  These results suggest that ursolic acid has the hepatoprotective actions. The inhibition of CCl4-induced liver fibrosis, inflammation and apoptosis by ursolic acid is due at least in part to its ability to modulate the Nrf2/ARE signalling pathway.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China. Electronic address: a1032042419@126.com.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology*; D004195:Disease Models, Animal; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D011897:Random Allocation; D015398:Signal Transduction; D014315:Triterpenes / Q000627:therapeutic use*; D000097245:Ursolic Acid
chemical_list: D051267:NF-E2-Related Factor 2; D014315:Triterpenes; D000097245:Ursolic Acid; C495636:Nfe2l2 protein, mouse