Furong Tongmai Capsule Ameliorates Atherosclerosis in ApoE-/- Mice by Modulating Gut Microbiota, Arachidonic Acid Metabolism and Macrophage Polarization.

Furong Tongmai capsule (FRTM) is a traditional Chinese medicine formula with reported lipid-lowering and anti-inflammatory activities, but its mechanisms in atherosclerosis (AS) remain unclear. In ApoE-/- mice fed a high-fat diet, FRTM administration improved serum lipid profiles by reducing total cholesterol, triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol. FRTM also attenuated aortic lesion formation, reduced pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), and improved oxidative stress indices. 16S rRNA sequencing showed that FRTM reshaped the gut microbiota, increasing beneficial taxa such as Lactobacillus and Bifidobacterium while decreasing Turicibacter. Functional prediction and untargeted serum metabolomics both suggested that arachidonic acid metabolism was a key pathway affected by FRTM. Furthermore, FRTM was associated with increased p-PPARγ and EP4 expression, decreased p-P65, and increased p-STAT3/STAT3, accompanied by downregulation of M1 markers (iNOS/Nos2) and upregulation of M2 markers (CD206 and ARG1). Faecal microbiota transplantation from FRTM-treated donors partially recapitulated the anti-atherosclerotic and anti-inflammatory effects. Overall, these findings suggest that FRTM may ameliorate AS in a murine model by modulating gut microbiota, arachidonic acid metabolism and macrophage polarization; however, further functional studies are needed to establish causality and assess translational relevance.