Anti-atherosclerosis effect of nobiletin via PINK1/Parkin-mediated mitophagy and NLRP3 inflammasome signaling pathway

The incidence of atherosclerosis (AS) is enormously increased, which becomes a serious public health problem. Nobiletin (NOB), a natural active substance of citrus, is found possessed abundant nutritional activities. However, the mechanism of anti-atherosclerosis effect of NOB has not been elucidated. Hences, the purpose of this study was to explore roles for NOB in AS. Macrophages and ApoE-/- mice models were used to investigate the anti-atherosclerotic effect and mechanism of NOB. The results indicated that NOB could modulate blood lipid metabolism and inflammation levels in mice, inhibit the formation of arterial plaques. Additionally, our data showed that mitophagy, inflammatory response, and cell pyroptosis were found in ApoE-/- mice after the treatment by NOB. The expression of key genes of PINK1/Parkin-mediated mitophagy were significantly up-regulated after treatment of NOB, while these of NLRP3 inflammasome were inhibited. Taken together, the underlying mechanism of NOB is to activate PINK1/Parkin-mediated mitophagy and suppress NLRP3-induced inflammasome production to provide an anti-atherosclerotic effect.