Osthole alleviates oxidized low-density lipoprotein-induced vascular endothelial injury through suppression of transforming growth factor-beta 1/Smad pathway

摘要

Osthole, a naturally-derived coumarin, has been shown to exhibit pharmacological activities including anti-inflammatory, anti-oxidative and cardiovascular protective effects. However, the effect of osthole on oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury and its underlying mechanism remain unknown. We found that osthole did not affect viability of human umbilical vein endothelial cells (HUVECs) but alleviated oxLDL-induced cytotoxicity in HUVECs. Osthole repressed ox-LDL-induced release of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, and IL-6 in HUVECs. Osthole reversed ox-LDL-induced elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) level, and reduction of superoxide dismutase (SOD) activity in HUVECs. Meanwhile, osthole attenuated ox-LDL-induced increase of mRNA expression and secretion of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Osthole increased nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) phosphorylation in ox-LDL-treated HUVECs. Furthermore, osthole inhibited ox-LDL-induced activation of the transforming growth factor-beta 1 (TGF-beta 1)/Smad pathway and activation of TGF-beta 1/Smad pathway by TGF-beta 1 attenuated the protective effects of osthole on HUVECs injury. These results suggested that osthole attenuated ox-LDL-induced HUVECs injury by inhibiting the TGF-beta 1/Smad pathway, suggesting that osthole might be a promising therapeutic agent for the treatment of atherosclerosis.