Magnolol Reduced TNF-alpha-Induced Vascular Cell Adhesion Molecule-1 Expression in Endothelial Cells via JNK/p38 and NF-kappa B Signaling Pathways

Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-alpha induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-alpha-treated HAECs. The decrease in VCAM-1 expression in response to TNF-alpha treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-kappa B activation and the translocation of HuR (an RNA binding protein) in TNF-alpha-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-alpha-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-alpha-induced JNK/p38 phosphorylation, HuR translocation, NF-kappa B activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses