Tao Luyuan, Gu Xingjian, Xu Enguo, Ren Shijia, Zhang Li, Liu Wenhua, Lin Xiaofeng, Yang Jianguang, Chen Changgong
Department of Cardiology, Taizhou First People's Hospital Taizhou 318020, Zhejiang, P. R. China.
Am J Transl Res. 2019 Jan 15;11(1):142-159. eCollection 2019.
Osthole, the main active constituents in traditional Chinese medicine fructus cnidii, has anti-inflammatory and anti-oxidant activities. Apoptosis of vascular endothelial cells is an important cause of cardiovascular disease. Inflammation and oxidative stress are two key factors in injury of endotheliocyte. In this study, we investigated the effect of osthole on Ang II-induced apoptosis of rat aortic endothelial cells (RAECs) and explored the underlying mechanisms. In the present study, the protective effects of osthole on RAECs induced by Ang II in vitro were tested. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to investigate the potential binding mode of osthole to NF-κB and Keap1. Our results showed osthole remarkably attenuates Ang II-induced apoptosis of RAECs via alleviating inflammation and oxidative stress. Molecular docking and MD simulations revealed the potential interaction of osthole bind to the P65 subunit of NF-κB and the Keap1 protein, an adaptor for the degradation of Nrf2. We further found that osthole decreased Ang II-induced inflammation and oxidative stress through respectively modulating NF-κB and Nrf2 pathways in RAECs. These studies provide evidence that osthole may represent a potential therapeutic agent for the treatment of vascular injury.
蛇床子素是传统中药蛇床子的主要活性成分，具有抗炎和抗氧化活性。血管内皮细胞凋亡是心血管疾病的重要原因。炎症和氧化应激是内皮细胞损伤的两个关键因素。在本研究中，我们研究了蛇床子素对血管紧张素II诱导的大鼠主动脉内皮细胞（RAECs）凋亡的影响，并探讨了其潜在机制。在本研究中，测试了蛇床子素对体外血管紧张素II诱导的RAECs的保护作用。此外，利用分子对接和分子动力学（MD）模拟研究了蛇床子素与NF-κB和Keap1的潜在结合模式。我们的结果表明，蛇床子素通过减轻炎症和氧化应激显著减轻血管紧张素II诱导的RAECs凋亡。分子对接和MD模拟揭示了蛇床子素与NF-κB的P65亚基和Keap1蛋白（Nrf2降解的衔接蛋白）的潜在相互作用。我们进一步发现，蛇床子素通过分别调节RAECs中的NF-κB和Nrf2途径，降低血管紧张素II诱导的炎症和氧化应激。这些研究提供了证据，表明蛇床子素可能是一种治疗血管损伤的潜在治疗剂。
