Investigating the anti-atherosclerotic effect and potential mechanism of Sanzi San in ApoE-defcient mice by UHPLC-ESI-QE-Orbitrap-MS based non-targeted metabonomics

CM), which is a well-known classic formula with an anti-atherosclerotic (AS) effect. However, the mechanism of SZS's anti-AS action remains to be further elucidated. This study went to check how well SZS works for AS and to dig deeper into how it might work. Our findings suggested that SZS significantly improved aortic lesion plaque areas of ApoE-/-mice. UHPLC-ESI-QE-Orbitrap-MS combined with pattern recognisable analysis, revealed a distinct separation between the model group and the control group, with the SZS-treated group being significantly closer to control than to model. This result was in line with the histopathological findings. Through metabolomics analysis, we found significantly different serum metabolites between groups, with 24 metabolites exhibiting significant regression. It is hypothesized that the anti-AS mechanism of SZS may be related to thiamine metabolism, arginine biosynthesis, and primary bile acid biosynthesis. The results of RT-qPCR showed that SZS alleviated AS by regulating the expression of Slc19a2, Tpk1, Ass1, Arg1, Cyp7a1 and Cyp8b1 in the pathway. Overall, these results provide initial support for the efficacy of SZS in the treatment of AS and investigate its potential pharmacological mechanisms, facilitating its rational development and application.