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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
Author(s) -
Chen YungHsiang,
Lin ShingJong,
Chen JawWen,
Ku HungHai,
Chen YuhLien
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704458
Subject(s) - magnolol , cell adhesion molecule , endothelium , cell adhesion , endothelial stem cell , vcam 1 , monocyte , microbiology and biotechnology , tumor necrosis factor alpha , intercellular adhesion molecule 1 , intercellular adhesion molecule , chemistry , immunology , pharmacology , biology , medicine , biochemistry , cell , in vitro , endocrinology , icam 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 endothelial‐leukocyte adhesion molecules and the activation of nuclear factor kappa B (NF‐κB) in tumour necrosis factor‐α (TNF‐α)‐treated human aortic endothelial cells (HAECs) were investigated. Pretreatment of HAECs with magnolol (5 μ M ) 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. Magnolol (5 and 10 μ M ) 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 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 2 O 2 generation in both control and TNF‐α treated HAECs. 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. 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 reduced adhesion of leukocytes. These results suggest that magnolol has anti‐inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory responses in vivo .British Journal of Pharmacology (2002) 135 , 37–47; doi: 10.1038/sj.bjp.0704458