Serum Pharmacochemistry and Metabolomics Reveal the Mechanism of Hedan Tablets Combined With Simvastatin in Hyperlipidemia Treatment

ABSTRACT Simvastatin (ST) is commonly used to treat hyperlipidemia (HLP), but it has serious side effects, such as myopathy and hepatotoxicity. Clinically, statins are often combined with Hedan tablets (HDT) to treat HLP, but the composition and mechanism of their pharmacological effects are still unclear. Therefore, the purpose of this study was to systematically explore the pharmacodynamic material basis and mechanism of HDT combined with ST in the treatment of HLP. Efficacy was assessed through serum lipid profiles and oxidative stress markers. The components entering the blood were identified by LC–MS. Metabolomic analyses were conducted using LC–MS and 1 H‐NMR techniques. Both single administration and combined administration have the effects of regulating blood lipids and oxidative stress, and the combination group showed significantly greater regulatory effects on TC, HDL‐C, and GSH‐Px than the simvastatin monotherapy group ( p < 0.05). Twenty components were successfully identified in blood. Metabolomics revealed 61 significantly altered metabolites in the combination group, mapped to nine key metabolic pathways including glycerophospholipid metabolism and citrate cycle.