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. In this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZW) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n=6), a probucol-supplemented (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 significantly reduced in the hematein-supplemented group and the probucol-supplemented group without changing plasma lipoprotein levels. Hematein and probucol prevented the up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCAM-1 and of monocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density lipoprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, hematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the present study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibition of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion development in the rabbit.
Oh
G T
GT
Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology, Yusong P.O. Box 115, 305-600, Taejon, South Korea.
Choi
J H
JH
Hong
J J
JJ
Kim
D Y
DY
Lee
S B
SB
Kim
J R
JR
Lee
C H
CH
Hyun
B H
BH
Oh
S R
SR
Bok
S H
SH
Jeong
T S
TS
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D029911:Caesalpinia; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006416:Hematoxylin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011341:Probucol / Q000494:pharmacology; D011817:Rabbits; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D000924:Anticholesteremic Agents; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D008055:Lipids; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; C007915:hematein; D011341:Probucol; D006416:Hematoxylin