Effects of Andrographis paniculata on Endocannabinoid Receptors in the Chronic Liver Injury Mice

Liver fibrosis is the result of chronic liver injury with the processes of oxidative stress, including hepatocyte apoptosis, inflammation and extracellular matrix remodeling . Endocannabinoid system has been found to play an important role in the liver diseases, such as liver fibrosis, ischemic/reperfusion injury, and vascular hyperdynamic change. There are two major G-coupled receptors of endocannabinoid, CB1 and CB2, have been found in the liver. CB1 is activated in the process of liver fibrosis which was reversed by CB1 antagonist. CB2 is activated in the liver injury to promote activated hepatic stellate cell apoptosis, and CB2 agonist may be an antifibrotic agent. Our previous study revealed that the expression of CB2 in the liver increased in the bile duct-ligated hamsters, and CB2 antagonist, AM630, protected from the liver injury through the effect of antioxidative stress. The water extract of Andrographis paniculata Nees also reversed the upregulation of CB2 in the liver due to cholestasis. Endocannabinoid and its receptors may have different roles between early and late stages of chronic liver injury, but the exact mechanisms are still unclear. The hepatic protective effects of Andrographis paniculata Nees through cannabinoid system are need to be determined. In the aims of first year, the relationship between early stage of liver injury and cannabinoid system will be determined, and the effects of Andrographis paniculata Nees on the cannabinoid system will be evaluated. The mechanisms Andrographis paniculata Nees on the oxidative stress and apoptosis through cannabinoid system in the liver should be determined. The profile of the expression of proteins in the liver and serum will be investigated through proteomic analysis. The animal models of early stage of chronic liver injury we use include mice with bile duct ligation for 1 week and TAA intraperitoneal injection for 4 weeks. In the second year, the roles of cannabinoid system and Andrographis paniculata Nees in the late stage of chronic liver injury will be investigated. The different roles of cannabinoid system in the early and late stages of chronic liver injury will be investigated. The animal models include bile duct ligation for 4 weeks and TAA intraperitoneal injection for 12 weeks. The signal transduction pathways regulated by Andrographis paniculata Nees will be evaluated through in vitro study of rat primary hepatocyte and stellate cells in the third year.

Project ID:PC9709-0205
External Project ID:NSC97-2320-B182-006-MY3