| Hepatic fibrosis results from the wound healing response to prolonged liver insult such as chronic hepatitis. It represents an imbalance of fibrogenesis and fibrolysis, causing formation of scars. Activation and proliferation of hepatic stellate cells (HSC) is a key to fibrogenesis while apoptosis of HSC is associated with resolution of fibrosis.;Treatment of chronic liver disease with herbal medicine has been documented in ancient China. Nowadays, practitioners of traditional Chinese medicine (TCM) also use herbs to treat chronic liver disease and it is conceivable that such herbs redress the imbalance between fibrogenesis and fibrolysis.;Intense efforts are currently underway to evaluate potential anti-fibrotic agents in herbal medicine. The study hypothesized that herbs may resolve hepatic fibrosis through induction of apoptosis of HSC. In this study, the anti-fibrotic potentials of fourteen commonly used herbs were examined. The anti-fibrotic effect and the underlying mechanism of two herbs were further investigated in an animal model.;Method. Fourteen herbs including Angelica sinensis(AS), Astragalus membranaceus(AM), Cordyceps sinensis(CS), Curcuma wenyujin(CW), Carthamus tinctorius(CT), Curcuma kwangsinensis(CK), Bupleurum chinensis(BC), Ligusticum chuanxiong(LC), Paeconia lactiflora(PL), Prunus persiea(PP), Poria cocos(PC), Salvia miltorrhiza(SM), Schisandra chinensis(SC) and Stephania tetrandra(ST) were selected for screening based on documented safety and effectiveness, and availability in commercial extracts. These two herbs were also authenticated by chemical profiling using HPLC.;Result. For in vitro bioassay, five herbs, namely Angelica sinensis (AS), Carthamus tinctorius (CT), Ligusticum chuanxiong(LC), Salvia miltiorrhiza(SM) and Stephania tetrandra(ST) demonstrated both anti-proliferative and pro-apoptotic activities in T6. SM and ST showed highest potencies with 51.63% and 44.52% of T6 cells showing apoptotsis respectively. Fas and Bax expression was up-regulated and BclxL expression decreased in HSC after incubation with SM and ST. Fas ligand and Bcl2 expression remained unchanged.;Both SM and ST reduced ALT elevation in rats in the prevention study. In the treatment study, ALT of all rats was resolved. Only ST reduced the fibrosis in both prevention and treatment studies. Maximum reduction of fibrosis compared to control was 44.12% in the prevention group and 56.83% in the treatment group. Activated HSC was decreased and apoptosis increased in rats with improved fibrosis.;Conclusion. ST prevented formation of liver fibrosis and promoted resolution of established fibrosis in the rat model. These effects were mediated through induction of HSC apoptosis in the liver. (Abstract shortened by UMI.)... |
