Luteolin protects HUVECs from TNF-α-induced oxidative stress and inflammation via its effects on the Nox4/ROS-NF-κB and MAPK pathways

Aim: inflammation and oxidative stress are now recognized to be two important contributing factors to the development of atherosclerosis (as). nadph oxidase-4 (nox4)-derived reactive oxygen species (ros),nf-κb and mapk play crucial roles in these processes. luteolin,a flavone rich in many plants,can interrupt the molecular expression and inhibit the progression of inflammation and oxidative stress. the present study was designed to test whether luteolin inhibits tnf-α-induced inflammation and oxidative stress in human umbilical vein endothelial cells (huvecs) and identify some of the mechanisms underlying these effects.methods: huvecs were treated with luteolin in the presence/absence of tnf-α. the mechanism of luteolin against tnf-α-induced cell injury was evaluated using western blotting,real-time rt-pcr and flow cytometry analyses.results: luteolin suppressed the tnf-α-activated ros generation,as well as the nox4,p22phox,and icam-1 and vcam-1 expression. luteolin also enhanced the bcl-2 and reduced caspase-3,-9 expression in the tnf-α-treated huvecs. finally,luteolin inhibited the tnf-α-induced transcriptional activity of nf-κb and p38 in addition to erk1/2 phosphorylation. the inhibitors and sirna of nox4 and nf-κb not only reduced ros generation,p38,erk1/2 phosphorylation and the icam-1 and vcam-1 expression,but also enhanced bcl-2 expression. the inhibitor of p38 had the same effect on the expression of icam-1,vcam-1 and bcl-2,while the inhibitor of erk1/2 increased the bcl-2 expression rather than reducing the icam-1 and vcam-1 expression.conclusions: luteolin attenuates tnf-α-induced oxidative stress and inflammation via its effects on the nox4/ros-nf-κb and mapk pathways. these results suggest that luteolin may provide a beneficial effect in treating vascular diseases associated with oxidative stress and inflammation. © 2014 japan atherosclerosis society.