Schinifoline attenuates atherosclerosis and modulates gut microbiota and bile acid metabolism in ApoE-/- mice.

Atherosclerosis (AS) remains a major global health burden despite advances in lipid-lowering therapies. Zanthoxylum bungeanum Maxim (ZBM) has demonstrated anti-atherosclerotic potential; however, the role of its active component, schinifoline (SF), in atherosclerosis remains unclear. In this study, we evaluated the anti-atherosclerotic effects of SF in high-fat diet (HFD)-fed ApoE-/- mice. SF treatment attenuated aortic plaque formation, improved serum lipid parameters, and decreased inflammatory responses. Integrated 16 S rRNA sequencing and untargeted metabolomics revealed that high-dose SF partially restored HFD-associated alterations in gut microbiota composition, including normalization of the Firmicutes/Bacteroidota ratio and changes in several atherosclerosis-associated genera, and altered bile acid profiles. In addition, SF reduced intestinal apical sodium-dependent bile acid transporter (ASBT) expression, suggesting a potential role in bile acid homeostasis. Collectively, these findings indicate that SF attenuates atherosclerosis and is associated with alterations in gut microbiota, bile acid profiles, and lipid and inflammatory responses, providing insights into its pharmacological effects.