Efficacy and Mechanism of Geniposide in the Treatment of Intrahepatic Cholestasis by Integration Analysis of Transcriptomic and Metabolomic

Geniposide is the main effective ingredient isolated from the fruit of Gardenia jasminoides, which plays an important role in hepatoprotection. However, the mechanism of which geniposide inhibits Intrahepatic Cholestasis (IC) is still uncertain. The purpose of this study was to explore the effect and pharmacological mechanism of geniposide on ANIT-induced IC. The rats were divided into control group, ANIT model group, geniposide (25, 50, 100mg/kg) and bifendate group. After 5 days of administration, except the control group, each groups were given ANIT for cholestasis liver injury. The protective effect of geniposide on IC was evaluated by detecting biochemical indexes, inflammatory factors and oxidative stress levels. Combined with metabolomics and transcriptomics, functional information was analyzed to reveal the pharmacological mechanisms. Molecular docking and immunoblotting were used to verify the active protein. Geniposide reduced serum ALT, AST, AKP, TBIL, DBIL and TBA caused by ANIT, and alleviated inflammation reaction and oxidative stress. It significantly enhanced the protein expression of OAT3, ABCG5, GST, NCEH1 and enriched in the bile secretion pathway and glutathione pathway. Geniposide has reflected its beneficial effects on liver injury which is expected to become a new strategy to prevent IC.