Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats.

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.
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.
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.
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).
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.
AuthorsQuanfang Huang, Yongwen Li, Shijun Zhang, Renbin Huang, Li Zheng, Ling Wei, Min He, Ming Liao, Li Li, Lang Zhuo, Xing Lin
JournalJournal of ethnopharmacology (J Ethnopharmacol) Vol. 143 Issue 3 Pg. 889-95 (Oct 11 2012) ISSN: 1872-7573 [Electronic] Ireland
PMID22967666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Antioxidants
  • Collagen Type III
  • Laminin
  • Madh3 protein, rat
  • RNA, Messenger
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Triterpenes
  • methyl helicterate
  • Hyaluronic Acid
  • Carbon Tetrachloride
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Hydroxyproline
  • Alanine Transaminase (blood)
  • Animals
  • Antioxidants (pharmacology, therapeutic use)
  • Aspartate Aminotransferases (blood)
  • Carbon Tetrachloride
  • Collagen Type III (blood)
  • Glutathione Peroxidase (metabolism)
  • Hyaluronic Acid (blood)
  • Hydroxyproline (metabolism)
  • Laminin (blood)
  • Lipid Peroxidation (drug effects)
  • Liver Cirrhosis (chemically induced, drug therapy, metabolism, pathology)
  • Male
  • Phytotherapy
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Smad3 Protein (genetics)
  • Sterculiaceae
  • Superoxide Dismutase (metabolism)
  • Transforming Growth Factor beta1 (genetics)
  • Triterpenes (pharmacology, therapeutic use)

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