Traditional Chinese medicine Yiqi Huoxue Huatan recipe inhibits atherosclerosis by regulating intestinal flora and its associated metabolites

Yiqi Huoxue Huatan recipe (YHHR) has been shown to possess anti-atherosclerotic effects, as detailed in various studies and clinical observations. However, the potential mechanism underlying atherosclerosis remains unclear. This study aimed to verify the effects of YHHR on gut microbiota composition and plasma metabolite levels in atherosclerotic mice and its mechanism of action. SPF apoE-/- mice were fed high-fat chow for 12 weeks to build an atherosclerosis model, Additionally, blank control group mice were fed normal chow, Mice were randomly assigned to the model group, low, medium and high dose YHHR group, antibiotic group and antibiotic + medium dose YHHR group. After three courses of drug administration, aortic plaques were observed by hematoxylin and eosin (HE) and Oil Red O staining, and mouse feces and serum were collected. The feces and serum of mice were analyzed using 16S rRNA sequencing, microbiological analysis, and targeted metabolomics. For cellular experiments, by constructing a foam cell model and applyingglycoursodeoxycholic acid(GUDCA)and Compound C interventions, WB was used to detect macrophage AMPK signaling pathway-related protein (AMPK) and efferocytosis-associated protein (ProS). YHHR was able to attenuate atherosclerotic plaque area, up-regulate the levels of gut bacteria Akkermansia muciniphila (A. muciniphila) and gut bacteria-associated metabolite bile acids GUDCA, and promote macrophage efferocytosis through the AMPK signaling pathway to exert anti-AS effects. YHHR may play a role in preventing atherosclerosis by influencing the production of the intestinal flora and its associated metabolites.