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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&amp;E staining. Human aortic endothelial cells (HAECs) were treated with KA, followed by hydrogen peroxide (H 2 O 2 ), to investigate the KA-mediated inhibition of ROS-induced oxidative stress and cell apoptosis. Oil Red O staining and H&amp;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 H 2 O 2 -induced death of HAECs and ROS generation. The H 2 O 2 -mediated upregulation of phosphorylated IKKβ, phosphorylated IκBα, and phosphorylated NF-κB was suppressed by KA. KA also reduced the Bax/Bcl-2 ratio and cleaved caspase-3 expression, preventing H 2 O 2 -induced vascular endothelial cell apoptosis. 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.

international journal of molecular sciences

Kansuinine A Ameliorates Atherosclerosis and Human Aortic Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Production and Suppressing IKKβ/IκBα/NF-κB Signaling