6-Shogaol Protects against Oxidized LDL-Induced Endothelial Injruries by Inhibiting Oxidized LDL-Evoked LOX-1 Signaling

الملخص EN

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-κB 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-κB, 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-κB 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.