Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 28, 2007; 13(8): 1214-1220
Published online Feb 28, 2007. doi: 10.3748/wjg.v13.i8.1214
Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model
Ming-Fu Yin, Li-Hua Lian, Dong-Ming Piao, Ji-Xing Nan
Ji-Xing Nan, Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education and College of Pharmacy, Yanbian University, Yanji 133002 Jilin Province, China
Ming-Fu Yin, Li-Hua Lian, College of Pharmacy, Yanbian University, Yanji 133002 Jilin Province, China
Dong-Ming Piao, Department of Pathology, the Affiliated Hospital, Medical College, Yanbian University, Yanji 133002 Jilin Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 32060127 and No. 30660225
Correspondence to: Dr. Ji-Xing Nan, Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education, Yanji 133002, Jilin Province, China. jxnanybu@gmail.com
Telephone: +86-433-2732456 Fax: +86-433-2659795
Received: November 27, 2006
Revised: December 15, 2006
Accepted: January 5, 2007
Published online: February 28, 2007
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-г.

RESULTS: In vitro study: 5, 10 or 25 μg/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-г 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.

Keywords: Tetrandrine, Apoptosis, Caspase-3, Liver fibrosis, Thioacetamide