Department of Pharmacy, Hengyang Central Hospital , Hengyang, Hunan Province, China.
Biosci Biotechnol Biochem. 2020 Oct;84(10):2104-2112. doi: 10.1080/09168451.2020.1787813. Epub 2020 Jun 28.
Oxidized low-density lipoprotein (ox-LDL) was known to induce endothelial cell injury to the progression of atherosclerosis (AS). Sophocarpine (SPC), a compound of sophora alkaloids isolated from the plant Sophora alopecuroides, has been shown to exhibit various pharmacological activities. This study was designed to investigate the protective effect of SPC on ox-LDL-induced endothelial cells and explored its underlying mechanism. Our results show that SPC pre-incubation ameliorated ox-LDL-mediated HAECs cytotoxicity, DNA fragmentation, and apoptosis in a dose-dependent manner. Moreover, SPC significantly downregulated the mRNA or protein expression level of pro-inflammatory mediators (TGF-β, IL-6, IL-1β, TNF-α) and pro-inflammatory vascular adhesion molecules (VCAM-1, ICAM-1, and E-selectin). Mechanistically, SPC pre-treatment downregulated IκBα expression and inhibited translocation of NF-κB in ox-LDL-mediated HAECs, overexpression of NF-κB p65 counteracted the cytoprotective and anti-apoptotic effect of SPC, suggesting that its action is dependent on NF-κB signaling pathway. Collectively, SPC suppresses ox-LDL-induced HAECs injury by inhibiting the NF-κB signaling pathway.
氧化型低密度脂蛋白(ox-LDL)可诱导内皮细胞损伤,进而促进动脉粥样硬化(AS)的进展。槐果碱(SPC)是从苦参中分离得到的一种苦参生物碱,已被证明具有多种药理活性。本研究旨在探讨 SPC 对 ox-LDL 诱导的内皮细胞损伤的保护作用及其作用机制。结果表明,SPC 预处理可呈剂量依赖性地改善 ox-LDL 介导的 HAECs 细胞毒性、DNA 片段化和细胞凋亡。此外,SPC 可显著下调促炎介质(TGF-β、IL-6、IL-1β、TNF-α)和促炎血管黏附分子(VCAM-1、ICAM-1 和 E-选择素)的 mRNA 或蛋白表达水平。机制上,SPC 预处理可下调 ox-LDL 介导的 HAECs 中 IκBα 的表达并抑制 NF-κB 的易位,过表达 NF-κB p65 可拮抗 SPC 的细胞保护和抗凋亡作用,表明其作用依赖于 NF-κB 信号通路。综上,SPC 通过抑制 NF-κB 信号通路抑制 ox-LDL 诱导的 HAECs 损伤。