Abstract
Corilagin, a polyphenolic tannic acid compound, showed significant anti-inflammatory activity in atherosclerotic mice. The present study aimed to evaluate the effect and mechanism of corilagin in atherosclerosis by in vivo, in vitro and in molecular docking strategies analysis. An atherosclerotic model was established by feeding ApoE-/- mice a high-fat diet. Murine RAW264.7 macrophages were cultured and induced with lipopolysaccharide (LPS). Treatment with corilagin had a marked inhibitory effect on the plaque area and lipid accumulation in atherosclerotic mice. Corilagin decreased the expression of iNOS and promoted the expression of CD206 in aortic plaque, as well as inhibited the production of proinflammatory factors in HFD-fed ApoE-/- mice and LPS-induced RAW264.6 cell. Corilagin also obviously inhibited the expression of TLR4, reduced the phosphorylation of the JNK, the protein expressions of p38 and NF-κB pathway. In addition, corilagin markedly diminished the nuclear translocation of NF-κBp65. Similarly, molecular docking study suggested that hydrogen bonds were detected between the corilagin and the five proteins (TLR4, Myd88, p65, P38, and JNK) with a significant "CDOCKER energy". These results showed that the antiatherosclerotic effect of corilagin against M1 macrophage polarization and inflammation via suppression the activation of TLR4-NFκB/MAPK signaling pathway. Therefore, corilagin could be a promising lead compound to develop drugs for the treatment of atherosclerosis.