Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
Evid Based Complement Alternat Med. 2013;2013:503521. doi: 10.1155/2013/503521. Epub 2013 Feb 19.
Endothelial dysfunction and oxLDL are believed to be early and critical events in atherogenesis. 6-Shogaol is the major bioactive compound present in Zingiber officinale and possesses the anti-atherosclerotic effect. However, the mechanisms remain poorly understood. The goal of this study was to investigate the effects of 6-shogaol on oxLDL-induced Human umbilical vein endothelial cells (HUVECs) injuries and its possible molecular mechanisms. Hence, we studied the effects of 6-shogaol on cell apoptosis, cellular reactive oxygen species (ROS), NF- κ B activation, Bcl-2 expression, and caspase -3, -8, -9 activities. In addition, E-selectin, MCP-1, and ICAM-1 were determined by ELISA. Our study show that oxLDL increased LOX-1 expression, ROS levels, NF- κ B, caspases-9 and -3 activation and decreased Bcl-2 expression in HUVECs. These alterations were attenuated by 6-shogaol. Cotreatment with 6-shogaol and siRNA of LOX-1 synergistically reduced oxLDL-induced caspases -9, -3 activities and cell apoptosis. Overexpression of LOX-1 attenuated the protection by 6-shogaol and suppressed the effects of 6-shogaol on oxLDL-induced oxidative stress. In addition, oxLDL enhanced the activation of NF- κ B and expression of adhesion molecules. Pretreatment with 6-shogaol, however, exerted significant cytoprotective effects in all events. Our data indicate that 6-shogaol might be a potential natural antiapoptotic agent for the treatment of atherosclerosis.
内皮功能障碍和氧化低密度脂蛋白（oxLDL）被认为是动脉粥样硬化形成的早期和关键事件。6-姜烯酚是生姜中主要的生物活性化合物，具有抗动脉粥样硬化作用。然而，其机制仍知之甚少。本研究旨在探讨 6-姜烯酚对 oxLDL 诱导的人脐静脉内皮细胞（HUVEC）损伤的作用及其可能的分子机制。因此，我们研究了 6-姜烯酚对细胞凋亡、细胞活性氧（ROS）、NF-κB 激活、Bcl-2 表达和 caspase-3、-8、-9 活性的影响。此外，通过 ELISA 测定 E-选择素、MCP-1 和 ICAM-1 的表达。我们的研究表明，oxLDL 增加了 LOX-1 的表达、ROS 水平、NF-κB、caspase-9 和 -3 的激活，并降低了 Bcl-2 的表达。这些变化被 6-姜烯酚减弱。6-姜烯酚与 LOX-1 的 siRNA 共同处理可协同降低 oxLDL 诱导的 caspase-9 和 -3 活性和细胞凋亡。LOX-1 的过表达减弱了 6-姜烯酚的保护作用，并抑制了 6-姜烯酚对 oxLDL 诱导的氧化应激的作用。此外，oxLDL 增强了 NF-κB 的激活和粘附分子的表达。然而，6-姜烯酚预处理对所有事件均发挥了显著的细胞保护作用。我们的数据表明，6-姜烯酚可能是治疗动脉粥样硬化的一种有潜力的天然抗凋亡剂。
