Conophylline Suppresses Hepatic Stellate Cells and Attenuates Thioacetamide-induced Liver Fibrosis in Rats

Background: Conophylline (CnP) is a vinca alkaloid purified from a tropical plant and inhibits activation of pancreatic stellate cells. Aim: We investi gated the effect of CnP on hepatic stellate cells (HSC) in vitro. We also e xamined whether CnP attenuates hepatic fibrosis in vivo. Method: We examin ed the effect of CnP on the expression of α-smooth muscle actin (α-SMA) and collagen-1, and apoptosis in Lx-2 cells. We also examined the e ffect of CnP on hepatic fibrosis induced by thioacetamide. Results: CnP red uced the expression of α-SMA and collagen-1. CnP promoted activation of caspase-3 and induced apoptosis. We then examined the effect of CnP on t hioacetamide-induced liver cirrhosis. In thioacetamide-treated rats, the su rface of the liver was irregular and multiple nodules were observed. Histol ogically, formation of pseudolobules surrounded by massive fibrous tissues w as observed. When CnP was administered together with thioacetamide, the sur face of the liver was smooth and liver fibrosis was markedly inhibited. Col lagen content was significantly reduced in CnP-treated liver. Conclusion: C nP suppresses HSC and induces apoptosis in vitro. CnP also attenuates forma tion of the liver fibrosis induced by thioacetamide in vivo.