Mechanism of Bile‐Processed Coptidis Rhizoma to Treat Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus Based on UPLC‐Q‐TOF/MS and Network Pharmacology

Abstract Bile‐processed Coptidis Rhizoma (DL) is a unique processed product of Coptidis Rhizoma in traditional Chinese medicines, it's commonly used in the treatment of type 2 diabetes (T2DM) or non‐alcoholic fatty liver disease (NAFLD) by folk Chinese physicians, but information about its active components and mechanism of action are still lacking. Network pharmacology combined with a molecular docking approach was used to screen for possible mechanisms to predict DL for treating NAFLD in T2DM. Validation of the effects of DL on key protein‐related effects such as anti‐inflammatory, antioxidant and insulin resistance inhibition through pharmacological assays. 32 components in DL were identified and 558 target targets were obtained. A total of 6165 targets related to T2DM, 5306 targets related to NAFLD were intersected with the component targets to obtain 329 common targets. PPI network analysis showed that 55 targets may be key targets for DL treatment of NAFLD inT2DM. Molecular docking showed that the components were well bound to the protein. The therapeutic effects of DL through anti‐oxidation, anti‐inflammation and alleviation of insulin resistance were validated based on animal studies. This study provides a solid basis and scientific rationale for the mechanism of DL and its application in the treatment of NAFLD in T2DM and other related diseases.