Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model

World J Gastroenterol. 2007 Feb 28;13(8):1214-20. doi: 10.3748/wjg.v13.i8.1214.

Abstract

Aim: To investigate the therapeutic effect of tetrandrine on liver fibrosis induced by thioacetamide in rats in vivo and in vitro.

Methods: In vitro study: we investigated the effect of tetrandrine on the apoptosis of rat hepatic stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the features of activated cells. In vivo study: hepatic fibrosis was induced in rats by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20 mg/kg for 4 wk compared with intraperitoneal injection of interferon-r.

Results: In vitro study: 5, 10 or 25 microg/mL of tetrandrine-induced activation of caspase-3 in t-HSC/Cl-6 cells occurred dose-dependently. In vivo study: tetrandrine treatment as well as interferon-r significantly ameliorated the development of fibrosis as determined by lowered serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil) and the levels of liver hydroxyproline (Hyp), hyaluronic acid (HA), laminin (LN) and also improved histological findings. The effects of tetrandrine at the concentration of 20 mg/kg were better than the other concentration groups.

Conclusion: Tetrandrine promotes the apoptosis of activated HSCs in vitro. Tetrandrine administration can prevent liver fibrosis and liver damage induced by thioacetamide in rats in vivo, indicating that it might exert a direct effect on rat HSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects*
  • Benzylisoquinolines / pharmacology
  • Benzylisoquinolines / therapeutic use*
  • Caspase 3 / drug effects
  • Extracellular Matrix / metabolism
  • Hydroxyproline / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • Organ Size
  • Rats
  • Rats, Wistar
  • Thioacetamide / pharmacology

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Benzylisoquinolines
  • Thioacetamide
  • tetrandrine
  • Caspase 3
  • Hydroxyproline