Kansuinine a ameliorates atherosclerosis and human aortic endothelial cell apoptosis by inhibiting reactive oxygen species production and suppressing ikkβ/iκbα/nf‐κb signaling

Abstract

Reactive oxygen species (ROS)‐induced vascular endothelial cell apoptosis is strongly associated with atherosclerosis progression. Herein, we aimed to examine whether Kansuinine A (KA), extracted from Euphorbia kansui L., prevents atherosclerosis development in a mouse model and inhibits cell apoptosis through oxidative stress reduction. Atherosclerosis development was analyzed in apolipoprotein E‐deficient (ApoE−/−) mice fed a high‐fat diet (HFD) using Oil Red O staining and H&E staining. Human aortic endothelial cells (HAECs) were treated with KA, followed by hydrogen peroxide (H2O2), to investigate the KA‐mediated inhibition of ROS‐induced oxidative stress and cell apoptosis. Oil Red O staining and H&E staining showed that atherosclerotic lesion size was significantly smaller in the aortic arch of ApoE−/− mice in the HFD+KA group than that in the aortic arch of those in the HFD group. Further, KA (0.1–1.0 μM) blocked the H2O2‐induced death of HAECs and ROS generation. The H2O2‐mediated upregulation of phosphorylated IKKβ, phos-phorylated IκBα, and phosphorylated NF‐κB was suppressed by KA. KA also reduced the Bax/Bcl‐ 2 ratio and cleaved caspase‐3 expression, preventing H2O2‐induced vascular endothelial cell apop-tosis. Our results indicate that KA may protect against ROS‐induced endothelial cell apoptosis and has considerable clinical potential in the prevention of atherosclerosis and cardiovascular diseases.