Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

摘要

Atherosclerosis is a chronic inflammatory disease characterized by increased expression of adhesion molecules, which contribute to monocytes adhesion to vascular endothelial cells (VECs). Paeonol, an active compound isolated from cortex Montan, has been shown to have therapeutic effects on atherosclerotic ani-mals. The present study aims to investigate whether paeonol can inhibit monocyte adhesion to vascular en-dothelial cells induced by oxidized Low-Density Lipoprotein (ox-LDL) and its possible therapeutic molecular mechanism. Exposure to ox-LDL (50, 100μg/mL) induced damaged to VECs leading to decreased survival rates (p<0.01). Paeonol (7.2-18.0μM) partially restored survival and reduced lactate dehydrogenase (LDH) release in VECs in a concentration-dependent manner (p<0.01). Adhesion of monocytes to VECs was dra-matically prevented by paeonol at 21.6 and 25.2μm (p<0.01). In addition, paeonol (14.4-21.6μM) repressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and lowered the levels of phosphor-c-Jun N-terminal kinase (P-JNK)1/2, phosphor-extracellular signal-regulated kinase (P-ERK)1/2 and P-p38 in a dose-dependent manner. The molecular effects of paeonol were more pronouced when companied with mitogen activated protein kinases (MAPKs) inhibitors. These data suggest that paeonol (10.8-25.2μm), at certain concentrations, prevents monocyte adhesion to VEC induced by ox-LDL., probably by means of blocking one or more target proteins on MAPKs signaling pathway. These results indicate that paeonol has potential pro-tective effects on the development of atherosclerosis.