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
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
复制标题
DOI：
10.1038/sj.bjp.0704458
复制
发表时间：
2002-01-01
影响因子：
7.3
通讯作者：
Chen, YL
中科院分区：
文献类型：
--
作者：
Chen, YH;Lin, SJ;Chen, YL
1在先前的研究中，我们发现厚朴酚，一种来自中国草药的有效抗氧化剂，减弱了胆固醇喂养的兔球囊损伤主动脉中单核细胞趋化蛋白-1（MCP-1）的表达和内膜增生。动脉内皮细胞粘附分子的表达和白细胞对内皮细胞的粘附可能在动脉粥样硬化中起主要作用。在本研究中，厚朴酚对内皮细胞-白细胞粘附分子表达及核因子κ B活化的影响肿瘤坏死因子-α中的NF-κ B研究了TNF-α处理的人主动脉内皮细胞（HAECs）。2用厚朴酚（5 μ m）预处理HAECs显著抑制TNF-α诱导的血管细胞粘附分子-1（VCAM-1）的表达。（64.8+/-1.9%），但对细胞间粘附分子-1和内皮细胞选择素的表达没有影响。3厚朴酚（5和10 μ M）显著降低人单核细胞系U937与TNF-α刺激的HAEC的结合（抑制率分别为58.4和56.4%）。使用P-32标记的NF-κ B共有序列作为探针的凝胶位移测定表明，厚朴酚预处理降低了TNF-α诱导活化后观察到的位移条带的密度。核提取物的免疫印迹分析和免疫荧光染色表明木兰酚处理的HAECs的核中NF-κ B p65的量减少58%。厚朴酚还减弱了对照和TNF-α处理的HAECs中细胞内H2 O2的产生。4此外，在体内，厚朴酚减弱了在胆固醇喂养的家兔的胸主动脉中观察到的内膜增厚以及TNF-α和VCAM-1蛋白的表达。5总之，这些数据表明，厚朴酚抑制TNF-α诱导的NF-κ B p65的核转位，从而抑制VCAM-1的表达，导致白细胞粘附减少。这些结果表明，厚朴酚具有抗炎作用，可能在预防动脉粥样硬化和炎症反应中发挥重要作用。
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-kappaB) in tumour necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs) were investigated.2 Pretreatment of HAECs with magnolol (5 mum) significantly suppressed the TNF-alpha-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 muM) significantly reduced the binding of the human monocytic cell line, U937, to TNF-alpha-stimulated HAECs (58.4 and 56.4% inhibition, respectively). Gel shift assays using the P-32-labelled NF-kappaB consensus sequence as probe showed that magnolol pretreatment reduced the density of the shifted bands seen after TNF-alpha-induced activation. Immunoblot analysis and immunofluorescence staining of nuclear extracts demonstrated a 58% reduction in the amount of NF-kappaB p65 in the nuclei in magnolol-treated HAECs. Magnolol also attenuated intracellular H2O2 generation in both control and TNF-a treated HAECs.4 Furthermore, in vivo, magnolol attenuates the intimal thickening and TNF-alpha and VCAM-1 protein expression seen in the thoracic aortas of cholesterol-fed rabbits.5 Taken together, these data demonstrate that magnolol inhibits TNF-alpha-induced nuclear translocation of NF-kappaB 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.