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

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, phosphorylated 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 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.