juglanin and Atherosclerosis

Atherosclerosis is characterized by endothelial cell dysfunction followed by lesion formation, arterial stenosis, potentially arterial occlusion, and severe outcomes. Novel treatments to slow or prevent the progression of the disease are of considerable clinical value. In the present study, we investigated the potential anti-atherosclerotic effects of the natural product juglanin in oscillatory shear stress (OSS) exposed endothelial cells.. Human aortic endothelial cells (HAECs) were exposed to OSS generated by a micro fluidal Teflon cone at 1 Hz frequency cycles (±5 dyn/cm. Juglanin reduces OSS-induced oxidative stress by reducing the production of ROS through downregulation of NOX-2 and rescuing OSS-induced reduced expression of eNOS. Juglanin also inhibits the inflammatory response by suppressing OSS-induced expressions of IL-1β, MCP-1, and HMGB1. Using THP-1 monocytes, we show that juglanin reduces the attachment of monocytes to endothelial cells by inhibiting the expression of VCAM-1 and E-selectin. Moreover, Juglanin rescues OSS-reduced expression of atheroprotective transcriptional factor KLF2.. Our findings indicate that juglanin protects against various atheroprone OSS-induced endothelial dysfunction. Juglanin has potential implication as a candidate for vascular intervention of atherosclerosis.

Topics: Atherosclerosis; Cell Adhesion; Cell Adhesion Molecules; Coculture Techniques; Cytokines; Endothelial Cells; Glycosides; Humans; Inflammation Mediators; Kaempferols; Mechanotransduction, Cellular; Monocytes; Oxidative Stress; Pulsatile Flow; Reactive Oxygen Species; Stress, Mechanical; THP-1 Cells