Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in hepatic stellate cells.

Background/Aims: Liver fibrosis represents a significant health problem worldwide. Hepatic stellate cells (HSCs) play a critical role in the live fibrosis. Rimonabant SR141716) is cannabinoid receptor type 1 (CB1) antagonist. The pharmacological effects of rimonabant on HSCs are not well characterized in HSCs. Methods: CB1 receptor was detected by immunohistochemistry in human liver fibrosis specimens. Cell proliferation as detected by MTT assay. Cell apoptosis, caspase-3 protein expression and cell cycle were detected by TEM and flow cytometry, respectively. Caspase-3 activity was measured using caspase-3 activity assay kit. Collagen secretion was evaluated by radioimmunoassay. CB1 receptor and signaling molecules were evaluated by qRTCR and Western blot. Results: Immunohistochemistry showed a discrete, punctuated CB1 immunoreactivity in kiuman liver fibrosis specimens. Rimonabant reduced HSC prOlikration and increased HSC apoptosis. Cl cycle analysis showed a decrease in G2/M phase cells and an increase in G0/G1 phase cells in HSC-T6 cells treated with rimonabant. Caspase-3 protein expressiol and activity were increased by rimonabant. Rimonabant decreased collagen secretion in HSC-T6 cells. Moreover rimonabant inhibited the expression of phosphorylated, FAK and ERK and down-regulated CB1 mRNA expression. Conclusion: The study provides new insights toward the pharmacological effect of rimonabant on HSCs in vitro. Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in HSCs.