title: Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats.
abstract: BACKGROUND
  Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its underlying mechanism.
  
  
  METHODS
  Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by intragastric administration with 2 ml/kg CCl(4) (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90 mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-β1 mRNA and Smad3 protein.
  
  
  RESULTS
  MH (33.45, 66.90 mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl(4). MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-β1 mRNA and Smad3 protein (P<0.05).
  
  
  CONCLUSIONS
  Our findings indicated that MH can inhibit CCl(4)-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-β-Smad3 signaling pathway.
authors.affiliation: First Affiliated Hospital of Guangxi Traditional Chinese Medicine University, Nanning 530023, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Li
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D024061:Collagen Type III / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D007797:Laminin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019660:Malvaceae; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D024061:Collagen Type III; D007797:Laminin; D012333:RNA, Messenger; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; C049014:methyl helicterate; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline