The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan.
Int J Mol Sci. 2021 Sep 24;22(19):10309. doi: 10.3390/ijms221910309.
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 L., prevents atherosclerosis development in a mouse model and inhibits cell apoptosis through oxidative stress reduction. Atherosclerosis development was analyzed in apolipoprotein E-deficient () 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 (HO), 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 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 HO-induced death of HAECs and ROS generation. The HO-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 HO-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.
活性氧（ROS）诱导的血管内皮细胞凋亡与动脉粥样硬化的进展密切相关。在此，我们旨在研究从 中提取的苦参碱 A（KA）是否可以通过降低氧化应激来预防高脂饮食喂养的载脂蛋白 E 缺陷（）小鼠模型中的动脉粥样硬化发展并抑制细胞凋亡。通过油红 O 染色和 H&E 染色分析高脂饮食（HFD）喂养的 小鼠的动脉粥样硬化发展。用 KA 处理人主动脉内皮细胞（HAEC），然后用过氧化氢（HO）处理，以研究 KA 对 ROS 诱导的氧化应激和细胞凋亡的抑制作用。油红 O 染色和 H&E 染色显示，与 HFD 组相比，HFD+KA 组小鼠的主动脉弓中动脉粥样硬化病变的大小明显更小。此外，KA（0.1-1.0 μM）阻断了 HO 诱导的 HAEC 死亡和 ROS 的产生。KA 还抑制了 HO 介导的磷酸化 IKKβ、磷酸化 IκBα 和磷酸化 NF-κB 的上调。KA 还降低了 Bax/Bcl-2 比值和 cleaved caspase-3 的表达，从而防止了 HO 诱导的血管内皮细胞凋亡。我们的结果表明，KA 可能防止 ROS 诱导的内皮细胞凋亡，并且在预防动脉粥样硬化和心血管疾病方面具有相当大的临床潜力。
