The protective effects of aloperine against ox-LDL-induced endothelial dysfunction and inflammation in HUVECs
The protective effects of aloperine against ox-LDL-induced endothelial dysfunction and inflammation in HUVECs
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DOI：
10.1080/21691401.2019.1699816
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发表时间：
2020-01-01
影响因子：
5.8
通讯作者：
Ren, Lina
中科院分区：
文献类型：
--
作者：
Li, Weiwei;Li, Yanshu;Ren, Lina
动脉粥样硬化是一种潜在威胁生命的心血管疾病，其特征是慢性内皮炎症和动脉粥样硬化病变的形成。已知循环中的氧化低密度脂蛋白通过触发氧化应激、炎症介质和黏附分子的表达以及下调动脉粥样硬化保护转录因子KLF2来诱导动脉粥样硬化。苦豆碱是从苦豆子属植物中分离得到的生物碱类化合物。在这里，我们采用不同的实验方法来确定苦豆碱对氧化低密度脂蛋白诱导的动脉粥样硬化标志物的影响。DHE染色显示苦豆碱可能通过降低细胞内ROS水平，挽救氧化低密度脂蛋白诱导的Noq-1和GCLC的减少，从而恢复HUVECs的氧化/抗氧化平衡。苦参碱治疗可降低ox-LDL诱导的IL-6、MCP-1、VCAM-1和E-选择素的表达，并挽救KLF2的减少。苦参碱还下调氧化低密度脂蛋白诱导的LOX-1表达。我们还证明了苦豆碱提高了细胞存活率，并抑制了U937单核细胞与HUVEC的黏附。最后，我们证明苦豆碱的作用是通过抑制P53蛋白的磷酸化来挽救KLF2的表达。综上所述，我们的结果暗示了苦杏仁碱作为一种安全有效的抗动脉粥样硬化治疗的潜力。
Atherosclerosis is a potentially life-threatening cardiovascular disease characterized by chronic endothelial inflammation and the formation of atherosclerotic lesions. Circulating ox-LDL is known to induce atherosclerosis by triggering oxidative stress, the expression of inflammatory mediators and adhesion molecules, as well as downregulating the atheroprotective transcriptional factor KLF2. Aloperine is an alkaloid compound isolated from the plant Sophora alopecuroides. Here, we employed various experimental methods to determine the effects of aloperine on ox-LDL-induced markers of atherosclerosis. DHE staining revealed that aloperine may restore the oxidant/antioxidant balance in HUVECs by reducing the level of ROS and rescuing the reduction in NOQ-1 and GCLC induced by ox-LDL. Aloperine treatment reduced ox-LDL-induced expression of IL-6, MCP-1, VCAM-1, and E-selectin and rescued the reduction in KLF2. Aloperine also downregulated ox-LDL-induced expression of the LOX-1. We also demonstrate that aloperine improved cell viability and inhibited the adhesion of U937 monocytes to HUVECs. Finally, we demonstrate that the effects of aloperine are mediated through the rescue of KLF2 expression via suppression of the phosphorylation of p53 protein. Together, our results implicate the potential of aloperine as a safe and effective antiatherosclerosis treatment.