Paeonol inhibits oxidized low density lipoprotein-induced monocyte adhesion to vascular endothelial cells by inhibiting the mitogen activated protein kinase pathway.
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 Moutan, has been shown to have therapeutic effects on atherosclerotic animals. The present study aims to investigate whether paeonol can inhibit monocyte adhesion to vascular endothelial cells induced by oxidized Low-Density Lipoprotein (ox-LDL) and its possible therapeutic molecular mechanism. Exposure to ox-LDL (50, 100 µg/mL) induced damaged to VECs leading to decreased survival rates (p<0.01). Paeonol (7.2-18.0 µM) 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 dramatically prevented by paeonol at 21.6 and 25.2 μM (p<0.01). In addition, paeonol (14.4-21.6 μM) 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 (10.8-25.2 μM), 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 protective effects on the development of atherosclerosis.
Key Laboratory of Xin'an Medicine, Ministry of Education, Experimental Center for Scientific Research, Hefei, Anhui, China.
Yue-Qin
YQ
Wang
Min
M
Dai
Ji-Chang
JC
Zhong
Deng-Ke
DK
Yin
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D029596:Paeonia / Q000737:chemistry*; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000098:Acetophenones; D004365:Drugs, Chinese Herbal; D008077:Lipoproteins, LDL; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; C013638:paeonol; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases