Fucoxanthin alleviated atherosclerosis by regulating PI3K/AKT and TLR4/NFκB mediated pyroptosis in endothelial cells

Fucoxanthin, a type of natural xanthophyll carotenoid, is mainly present in seaweeds and various microalgae. This compound has been proved to possess multiple functions including antioxidation, anti-inflammation and anti-tumor. Atherosclerosis is widely deemed as a chronic inflammation disease, and as the basis of vascular obstructive disease. However, there is rare research about fucoxanthin's effects on atherosclerosis. In this study, we demonstrated that the plaque area of mice treated with fucoxanthin was significantly reduced compared to the group that did not receive fucoxanthin. In addition, Bioinformatics analysis showed that PI3K/AKT signaling might be involved in the protective effect of fucoxanthin, and this hypothesis was then verified in vitro endothelial cell experiments. Besides, our further results showed that endothelial cell mortality measured by TUNEL and flow cytometry was significantly increased in the oxidized low-density lipoprotein (ox-LDL) treatment group while significantly decreased in the fucoxanthin treatment group. In addition, the pyroptosis protein expression level in the fucoxanthin group was significantly lower than that in the ox-LDL group, which indicated that fucoxanthin improved the pyroptosis level of endothelial cells. Furthermore, it was revealed that TLR4/NFκB signaling were also participated in the protection of fucoxanthin on endothelial pyroptosis. Moreover, the protection of fucoxanthin on endothelial cell pyroptosis was abrogated when PI3K/AKT was inhibited or TLR4 was overexpressed, which further suggested the anti-pyroptosis effect of fucoxanthin was mediated through regulations of PI3K/AKT and TLR4/NFκB signaling.