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- Title
Magnolol attenuates VCAM-1 expression in vitro in TNF-α-treated human aortic endothelial cells and in vivo in the aorta of cholesterol-fed rabbits.
- Authors
Yung-Hsiang Chen; Shing-Jong Lin; Jaw-Wen Chen; Hung-Hai Ku; Yuh-Lien Chen
- Abstract
1 In a previous study, we showed that magnolol, a potent antioxidant derived from a Chinese herb, attenuates monocyte chemotactic protein-1 (MCP-1) expression and intimal hyperplasia in the balloon-injured aorta of cholesterol-fed rabbits. Expression of cell adhesion molecules by the arterial endothelium and the attachment of leukocytes to the endothelium may play a major role in atherosclerosis. In the present study, the effects of magnolol on the expression of endothelialleukocyte adhesion molecules and the activation of nuclear factor kappa B (NF-κB) in tumour necrosis factor-α (TNF-γ)-treated human aortic endothelial cells (HAECs) were investigated. 2 Pretreatment of HAECs with magnolol (5 µM) significantly suppressed the TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) (64,8 ± 1.9%), but had no effect on the expression of intercellular cell adhesion molecule-1 and endothelial cell selectin. 3 Magnolol (5 and 10 µM) significantly reduced the binding of the human monocytic cell line, U937, to TNF-α-stimulated HAECs (58.4 and 56.4% inhibition, respectively). Gel shift assays using the [sup 32]P-labelled NF-κB consensus sequence as probe showed that magnolol pretreatment reduced the density of the shifted bands seen after TNF-α-induced activation. Immunoblot analysis and immunofluorescence staining of nuclear extracts demonstrated a 58% reduction in the amount of NF-κB p65 in the nuclei in magnolol-treated HAECs. Magnolol also attenuated intracellular H[sub 2]O[sub 2] generation in both control and TNF-α treated HAECs. 4 Furthermore, in vivo, magnolol attenuates the intimal thickening and TNF-α and VCAM-1 protein expression seen in the thoracic aortas of cholesterol-fed rabbits. 5 Taken together, these data demonstrate that magnolol inhibits TNF-α-induced nuclear translocation of NF-κB p65 and thereby suppresses expression of VCAM-1, resulting in ...
- Publication
British Journal of Pharmacology, 2002, Vol 135, Issue 1, p37
- ISSN
0007-1188
- Publication type
Academic Journal
- DOI
10.1038/sj.bjp.0704458