Tussilagone attenuates atherosclerosis through inhibiting MAPKs-mediated inflammation in macrophages.

Atherosclerosis is a common chronic inflammatory disease. Recent studies have highlighted the key role of macrophages and inflammation in process of atherosclerotic lesion formation. A natural product, tussilagone (TUS), has previously exhibited anti-inflammatory activities in other diseases. In this study, we explored the potential effects and mechanisms of TUS on the inflammatory atherosclerosis. Atherosclerosis was induced in ApoE mice by feeding them with a high-fat diet (HFD) for 8 weeks, followed by administration of TUS (10, 20 mg ·kg·d, i.g.) for 8 weeks. We demonstrated that TUS alleviated inflammatory response and reduced atherosclerotic plaque areas in HFD-fed ApoE mice. Pro-inflammatory factor and adhesion factors were inhibited by TUS treatment. In vitro, TUS suppressed foam cell formation and oxLDL-induced inflammatory response in MPMs. RNA-sequencing analysis indicated that MAPK pathway was related to the anti-inflammation and anti-atherosclerosis effects of TUS. We further confirmed that TUS inhibited MAPKs phosphorylation in plaque lesion of aortas and cultured macrophages. MAPK inhibition blocked oxLDL-induced inflammatory response and prevented the innately pharmacological effects of TUS. Our findings present a mechanistic explanation for the pharmacological effect of TUS against atherosclerosis and indicate TUS as a potentially therapeutic candidate for atherosclerosis.