Auricularia heimuer Ameliorates Oxidative Stress and Inflammation to Inhibit Atherosclerosis Development in ApoE−/− Mice

<b>Background:</b> Atherosclerosis is a chronic vascular disease triggered by lipid accumulation. <i>Auricularia heimuer</i> is rich in various bioactive compounds that have anti-inflammatory, antioxidant, and hypolipidemic properties. The specific beneficial effects of <i>A. heimuer</i> on atherosclerosis and its underlying mechanisms require further investigation. <b>Methods</b>: In this study, ApoE^-/- mice were utilized as models of atherosclerosis induced by a high-fat diet (HFD) to investigate the effects of <i>A. heimuer.</i> Analyses of gut microbiota and serum metabolomics were conducted to elucidate the potential mechanism. <b>Results:</b> In HFD-fed ApoE^-/- mice, <i>A. heimuer</i> significantly inhibited the increase in body weight, regulated lipid levels, and alleviated aortic lesions. <i>A. heimuer</i> also modulated the abundance of intestinal flora such as <i>Akkermansia</i> and <i>Ruminococcus</i> and altered the levels of serum metabolites, including 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) and N-acetyl galactosamine 4-sulfate. Furthermore, <i>A. heimuer</i> alleviated oxidative stress and inflammatory responses, thereby mitigating atherosclerosis via the Nrf2/NF-κB signaling pathway. <b>Conclusions:</b> These findings suggest that <i>A. heimuer</i> may serve as a potential therapeutic strategy for atherosclerosis.