Modulation of Ger-Gen-Chyn-Lian-Tang on Hepatic Bile Acid Homeostasis and Ubiquitin Proteasome System in High-Fat Diet Induced Non-Alcoholic Fatty Liver Disease and Farnesoid X Receptor-Deficient Hepatocellular Carcinoma Mice

Non-alcoholic fatty liver disease (NAFLD) or farnesoid X receptor-deficiency mice has been shown to develop spontaneous liver cancer. The incidence of NAFLD has increased significantly in recent years, and has become a major cause of liver cancer. Ger-Gen-Chyn-Lian-Tang (GGCLT) is a traditional Chinese medicine prescription for treating chronic hepatitis, various types of enteritis, but there is no detailed research on the efficacy for NAFLD, especially lack of evidences on the hemostasis of bile acid in the enterohepatic circulation. Indeed, according to our previous results, GGCLT does have hepato-protection effects on liver damage models. However, the modulation of GGCLT on hepatic lipogenesis and farnesoid X receptor-mediated bile acids metabolism and synthesis has not been clearly addressed. In addition, the potential role of GGCLT in the control of hepatic ubiquitin-proteasome system and bile homeostasis of farnesoid X receptor-deficiency state has never addressed. This project sets the primary objective to analyze the positive role of GGCLT in the dynamic disturbance of bile acid in different animal models of chronic liver diseases. The secondary objective to be established a functional test to evaluate the regulation of GGCLT on the ubiquitin-proteasome system and bile acid homeostasis, as well as gut microbiota composition. Finally, the third end of this project can show the characteristics of GGCLT may have the FXR agonist mimic effects on FXR activation and the bile acid-dependent mechanisms in the intestinal microbial flora. The importance of this project not only shows that GGCLT can be used as an adjuvant therapy for the treatment of NAFLD, but also provide the precise mechanisms to illustrate with GGCLT has metabolic pathways on the enterohepatic bile acid circulation and ubiquitin-proteasome. That’s made a new direction for traditional Chinese medicine in the treatment of NAFLD.

Project ID:PC10907-1229
External Project ID:MOST109-2320-B182-023-MY3