Targeted Screening Of Herbal Medicine Yin-zhi-huang For Protecting Against Cholestatic Liver Injury And Modulating Bile Acid Metabolism

Yin-zhi-huang, a typical Chinese multi-herb formulation, represents a traditional treatment for neonatal jaundice and chronic liver diseases.Yin-zhi-huang is widely used for intrahepatic cholestasis in East Asian countries, but its active components, the regulation of pharmacokinetics and the pharmacodynamic mechanism remain unknown. Therefore, the herbal medicine Yin-zhi-huang is screened both for modulating bile acid metabolism and for protecting against cholestatic liver injury.In this study, we develope a mouse model for intrahepatic cholestasis to explore the specifiic mechanism of drug actions. The data showed chlorogenic acid and geniposide protected against theɑ-naphthylisothiocyanate(ANIT)-induced liver injury via STAT3 and NFκB signaling. In addition, the influence of other components on the CYP450 enzymes expression were analyzed. These data provided new insights into the traditional Chinese medicines.The main research contents of thesis are as follows:1. The targeted screening of Yin-zhi-huang for protecting against cholestatic liver injury and drug metabolizing enzymes expression: A mouse model was develop for intrahepatic cholestasis, and the state, phenotype, biochemical indices,pathological analysis were used to analyses four main active components chlorogenic acid, geniposide, baicalin and scoparone.The data showed chlorogenic acid and geniposide can improve the liver damage and cholestasis effectively. Also, the influence of monomer on the expression of CYP450 enzyme was analyse,the results indicated CYP2 B and CYP2 C expression were induced, and may cause drug-drug interactions.2. The liver protection mechanism of chlorogenic acid. The Q-PCR analysis was used to explore the expression of inflammation, bile acid metabolism-related genes, the data showed the mechanism may related with inflammatory factors, and western blot revealed that chlorogenic acid inhibited the activation and expression of STAT3 as well as those of NFκB.3. The mechanism of geniposide protect against liver injury. The mechanism of geniposide was explored via the Q-PCR and western blot analysis, the result revealed that geniposide inhibited the activation and expression of STAT3 and NFκB.