Edaravone Ameliorate Inflammation in Vitamin D3 and High Fat Diet Induced Atherosclerosis in Rat via Alteration of Inflammatory Pathway and Gut Microbiota

ABSTRACT Cardiovascular disease refers to a group of conditions that affect the heart and blood vessels, including coronary artery disease, heart failure, and stroke, among others. Edaravone (ED) inhibits oxidative stress and free radical damage, which are thought to contribute to the progression of various diseases. Thus, the purpose of the study is to examine the cardioprotective effect of ED against vitamin D 3 and high fat‐induced atherosclerosis in rats. In this study, Sprague Dawley (SD) rats were utilized. The rats were separated into several groups and fed a high‐fat diet along with vitamin D 3 to induce atherosclerosis. Various doses of ED were orally administered to the animals for 30 days. The administration of Edaravone effectively reduced the elevated body weight, as well as the excessive water and food consumption. The treated groups exhibited a decrease in glucose level, leptin, and apolipoprotein‐B. Administration of ED also modified the cholesterol parameters, coronary artery index, atherogenic index, and antioxidant parameters. It also reduced the elevated heart rate, systolic blood pressure (BP), mean BP, and diastolic BP. The group treated with ED exhibited a decrease in the level of inflammatory cytokines. The ED significantly ( p < 0.001) reduced the levels of MMP‐2, MMP‐3, and MMP‐9. Furthermore, it induced significant ( p < 0.001) adjustments in the abundance of Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, and F/B ratio. Edaravone exhibited the cardio protection against HFD induced atherosclerosis in rats via alteration of gut microbiota.