Atherosclerosis 159 (2001) 17 – 26 Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression Goo Taeg Oh a , Jae Hoon Choi b , Jung Joo Hong a , Dae-Young Kim b , Sae-Bom Lee c , Ju-Ryoung Kim c , Chul-Ho Lee a , Byung-Hwa Hyun a , Sei Ryang Oh d , Song-Hae Bok c , Tae-Sook Jeong c, * a Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology, Yusong P.O. Box 115, Taejon 305 -600, South Korea b Department of Pathology, College of Veterinary Medicine, Seoul National Uniersity, Suwon 440 -744, South Korea c Cardioascular Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong P.O. Box 115, Taejon 305 -600, South Korea d Immunomodulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong P.O. Box 115, Taejon 305 -600, South Korea Received 2 October 2000; received in revised form 31 January 2001; accepted 1 February 2001 Abstract 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-supple- mented (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  (TNF-) 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-B in HUVECs stimulated with TNF-. 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. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hematein; Atherosclerosis; MCP-1; VCAM-1 www.elsevier.com/locate/atherosclerosis 1. Introduction Atherosclerosis is a chronic inflammatory vascular disease that accounts for the majority of human coro- nary artery disease and stroke. Histopathologically, atherosclerosis is characterized by a thickening of the vascular wall called ‘atheroma’ due to lipid accumula- tion and infiltration of macrophages and lymphocytes [1,2]. The recruitment of circulating monocytes into the intima is a key event in early atherogenesis. The vascu- lar adhesion molecule 1 (VCAM-1), which interacts with the monocyte intergrin VLA-4 [3], is assumed to play an important role in the adhesion of monocytes to the endothelium. VCAM-1 is expressed on endothelial cells overlying early fatty streaks of rabbits [4–8] and at sites of inflammation in human arteries [9,10]. In addi- tion, VCAM-1 is expressed by vascular smooth muscle * Corresponding author. Tel.: +82-42-8604558; fax: +82-42- 8612675. E-mail address: tsjeong@mail.kribb.re.kr (T.-S. Jeong). 0021-9150/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(01)00464-6