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^-1·d^-1, 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.