Possible Mechanisms of Ger-Gen-Chyn-Lian-Tang on Hepatic Endocannabinoid Receptors and Hypoxia-Inducing Factor in Experimental Liver Fibrosis Mice

Hepatic fibrosis is a multistage process with multi-factorial etiology. The endocannabinoid system is an important regulator of hepatic fibrosis associated with chronic liver diseases. On the other hand, Ger-Gen-Chyn-Lian-Tang (GGCLT) has been shown to have biological effects including antibacterial, antioxicant and anti-inflammation. In our recent studies of GGCLT, we have demonstrated that hepatoprotection properties of GGCLT, mediating hepatic fibrosis-related signallings, and the consequent against hepatic oxidative stress events associated with enhance hepatic GSH levels. The objective of current proposal, we will perform the studied of molecular mechanisms of biological function of GGCLT on cannabinoids receptors-mediated signalling cascade, which related to chronic liver injury in animal models. Briefly, in Specific Aim I, we will clarify CB receptors-dependent specific signaling pathways, involving in GGCLT attenuation for hepatic damage. Specifically, we will set up the functional assay to examine and evaluate the GGCLT in the regulation of hepatic apoptosis and oxidative stress-related gene including inflammatory cytokine. Moreover, identity the specific mechanisms upon the endocannabinoid system will be set as check points in this project. In Specific Aim II, we will use different liver injury models to dissect the potential role of GGCLT in cannabinoid-mediated chronic liver injury progression. The possible protein profiles in tissues that are associated with the pathological change during liver injury progression will be analyzed by immunohistochemistry and Western blotting approaches. Real-Time RT-PCR will be used to confirm the differentially expressed pattern of related proteins form above analysis. In Specific Aim III, Hypoxia inducible factor, which steadily and be regulated in CB receptors-dependent conditions. We further identity CB receptors-dependent signaling involving in hypoxia-mediated hepatic angiogenesis and inflammatory response after GGCLT treatment to confer the modulations of GGCLT on fibrosis which were induced by liver damage. This study would fill a long-existing gap in liver disorder of hepatic research. It may also lead to discovery of herbal medicine participating in maintaining endogenous cannabinoid receptors signalling homeostasis. Completion of this focused project, we will define signal transduction pathways mediated by cannabinoid receptors to hepatic fibrosis or angiogenesis. Moreover, we will elucidate cellular and molecular mechanisms by which the potential therapeutic role of GGCLT in chronic liver injury.

Project ID:PC10308-0979
External Project ID:MOST103-2320-B182-002-MY3