Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression

Hematein is a compound isolated from Caesalpinia sappan that has been used in oriental medicine as both an analgesic and an anti-inflammatory agent. I n this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZ)V) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n = 6), a probucol-supp lemented (0.25% in diet) group (n = 6), and a control group (n = 6). After 8 weeks of treatments, the extent of the atherosclerotic lesions was signif icantly reduced in the hematein- supplemented group and the probucol-supple mented group without changing plasma lipoprotein levels. Hematein and probu col prevented the up-regulation of the vascular cell adhesion molecule-1 (V CAM- 1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCA M-1 and of 1-nonocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density li poprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, h ematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the presen t study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibit ion of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion d evelopment in the rabbit. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.