title: 6-Shogaol Protects against Oxidized LDL-Induced Endothelial Injruries by Inhibiting Oxidized LDL-Evoked LOX-1 Signaling.
abstract: 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.
authors.affiliation: Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
authors.forename: Yun Kai
authors.initials: YK
authors.lastname: Wang
authors.forename: Ya Jun
authors.initials: YJ
authors.lastname: Hong
authors.forename: Yong Hua
authors.initials: YH
authors.lastname: Yao
authors.forename: Xiao Min
authors.initials: XM
authors.lastname: Huang
authors.forename: Xue Bo
authors.initials: XB
authors.lastname: Liu
authors.forename: Chun Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoliang Leon
authors.initials: XL
authors.lastname: Xu