Rabdosia serra alleviates intrahepatic cholestasis via activation of the CAR/MRP2 pathway in a rat model

Objectives This study aimed to investigate the pharmacological effects and mechanisms of Xihuangcao (XHC) in a rat model of Intrahepatic cholestasis (IC). Methods Network pharmacology analysis was conducted to identify the main active ingredients and key targets of XHC in alleviating IC, validated through molecular docking. An IC rat model was then established to evaluate the efficacy of XHC. The potential mechanisms were verified using hematoxylin-eosin (HE) staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting (WB). Results Network analysis identified CAR as the key target for XHC’s effects on IC, with active ingredients including luteolin, quercetin, isorhamnetin, kaempferol, a quercetin derivative, and skrofulein. Molecular docking confirmed the strong binding affinity of these components to CAR. Compared to the model group, high-dose XHC significantly increased the body weight of rats (p<0.01), and decreased serum biochemical markers related to IC, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin levels (p<0.01). HE staining showed reduced hepatocyte necrosis and inflammation. Additionally, RT-qPCR and WB confirmed increased mRNA and protein levels of MRP2 and CAR in the high-dose XHC group (p<0.001). Conclusions XHC may alleviate IC through the CAR/MRP2 signaling pathway, providing pharmacological support for its use in treating IC.