The Efficacy of Hesperidin in the Reduction of Atherosclerosis in ApoE−/− Mice and Its Possible Mechanism of Action

Atherosclerosis (AS) currently lacks fully effective treatments. This study investigated the natural compound hesperidin as a potential therapy. Apolipoprotein E knockout (ApoE^-/-) mice were used as a model of atherosclerosis; we found that hesperidin treatment improved physiological and metabolic health, reduced plaque formation, and decreased systemic inflammation and oxidative stress. Hesperidin also reshaped gut microbiota, increasing beneficial bacteria (<i>Verrucomicrobia</i> and <i>Bacteroidota</i>) and significantly lowering fecal levels of branched-chain amino acids (BCAAs: valine, leucine, and isoleucine) by 27.4%, 50.1%, and 40.8%, respectively. These changes were linked to specific microbial shifts. We conclude that hesperidin alleviates atherosclerosis likely by modulating the gut microbiota-BCAA-host axis, identifying it as a promising dietary intervention or therapeutic agent.