Effects of Hedan Tablets Combined With Simvastatin on Hyperlipidemia: Insights From Microbiomics and Metabolomics

Simvastatin (ST) has limited long-term clinical utility due to its adverse effects. The combination of Hedan tablets and simvastatin (HST) exhibits superior lipid-lowering effects, but its mechanism remains unclear. This study aims to investigate the effects of HST in hyperlipidemic rats based on 16S rRNA gene sequencing and metabolomics. Gut microbiota composition was analyzed by 16S rRNA sequencing; fecal short-chain fatty acids (SCFAs) and bile acids (BAs) in the liver and serum were quantified by GC-MS and LC-MS, respectively; and hepatic BA metabolism-related gene expression was detected by RT-qPCR. 16S rRNA sequencing revealed that HST influenced gut microbiota composition and increased microbial diversity. Compared with ST, the effect of HST on SCFA levels was primarily reflected in elevated propionic acid and isovaleric acid levels, with total SCFA content significantly higher than that in the MOD group (p < 0.001). RT-qPCR results showed that HST-mediated BA regulation involved the upregulation of hepatic BA synthesis genes (CYP8B1 and BACS) and the transport gene (MRP2), as well as the downregulation of reabsorption genes (NTCP and ASBT) (p < 0.001). This study suggests that the ameliorative effect of HST on hyperlipidemia is associated with the regulation of gut microbiota and its metabolites (SCFAs and BAs).