Sini San ameliorates cholestatic liver injury by intrahepatically activating PPARα

Objective To investigate the therapeutic effects of Sini San (SNS) in cholestatic mice, and to elucidate underlying mechanisms and bioactive ingredients. Methods Through a metabolomics approach, this study identified bioactive components in SNS that were absorbed into the bloodstream. Transcriptomics were performed to identify intrahepatic targets of SNS. Results These findings demonstrated that SNS significantly attenuated partial bile duct ligation (pBDL)-induced cholestatic liver injury by activating intrahepatic (peroxisome proliferator-activated receptor alpha, PPAR α ). SNS-mediated PPAR α activation significantly modulated the expression of bile acid transporters to facilitate intrahepatic bile acid homeostasis and simultaneously ameliorates hepatic inflammation. This study identified marmin, astilbin, poncirin, and isosinensetin as potential PPAR α agonists among absorbed SNS components. Subsequently, PPAR α inhibitor (GW6471), significantly abolished the regulative effects of SNS on lipid and bile acid metabolism. Conclusion This research not only underscores the regulative role of PPAR α in bile acid metabolism but also indicates the presence of potential PPAR α agonists in SNS, offering a novel therapeutic strategy for treating cholestatic liver disease.