Role of EGFR/ErbB2 and PI3K/AKT/e-NOS in Lycium barbarum polysaccharides Ameliorating Endothelial Dysfunction Induced by Oxidative Stress

Abstract

Lycium barbarum polysaccharides (LBP) are the major ingredients of wolfberry. In this study, we investigated the role of LBP in endothelial dysfunction induced by oxidative stress and the underlying mechanisms using thoracic aortic endothelial cells of rat (RAECs) as a model. We found that Ang II inhibits cell viability of RAECs with 10${}^{-6}$$$mol/L of Ang II treatment for 24$$h most potential ($P<0.05$), the level of reactive oxygen species (ROS) is increased by Ang II treatment ($P<0.01$), and the expression of Occludin and Zonula occludens-1 (ZO-1) is decreased by Ang II treatment ($P<0.05$). However, preincubation of cells with LBP could inhibit the changes caused by Ang II, LBP increased cell viability ($P<0.05$), decreased the level of ROS ($P<0.01$), and up-regulated the expression of Occludin ($P<0.05$) and ZO-1. In addition, Ang II treatment increased the expression of EGFR and p-EGFR (Try1172) and which can be inhibited by LBP. On the contrary, expression of ErbB2, p-ErbB2 (Try1248), PI₃K, p-e-NOS (Ser1177) ($P<0.05$), and p-AKT (Ser473) ($P<0.05$) was inhibited by Ang II treatment and which can be increased by LBP. Treatment of the cells with inhibitors showed that the regulation of p-e-NOS and p-AKT expression by Ang II and LBP can be blocked by PI₃K inhibitor wortmannin but not EGFR and ErbB2 inhibitor AC480. Taken together, our results suggested that LBP plays a critical role in maintaining the integrality of blood vessel endothelium through reduced production of ROS via regulating the activity of EGFR, ErbB2, PI₃K/AKT/e-NOS, and which may offer a novel therapeutic option in the management of endothelial dysfunction.

Keywords: EGFR; Endothelial Dysfunction; ErbB2; LBP; Oxidative Stress; PI3K/AKT/e-NOS.