Cardiovascular protective effects of synthetic isoflavone derivatives in apolipoprotein E-deficient mice

被引:22
作者
Jiang, F [1 ]
Jones, GT
Husband, AJ
Dusting, GJ
机构
[1] Univ Melbourne, Howard Florey Inst, Melbourne, Vic 3010, Australia
[2] Univ Otago Sch Med, Dept Surg, Vasc Res Grp, Dunedin, New Zealand
[3] Novogen Ltd, Sydney, NSW, Australia
关键词
antioxidant; apolipoprotein E-deficient; atherosclerosis; endothelial dysfunction; endothelium-dependent vasorelaxation; flavonoids; hyperlipidemia; isoflavone; nitric oxide; oxidative stress;
D O I
10.1159/000071891
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Dietary flavonoids are thought to protect against cardiovascular disease. We have studied the effects of bioactive isoflavone metabolites on hyperlipidemia, endothelial dysfunction and the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(0)) mice fed a Western high-fat diet. Supplementation with dihydrodaidzein (DiD), dehydroequol (DeE) (both 25 mg kg(-1). day(-1)) and their combination (D/D; 12.5 mg kg(-1.)day(-1) for each) for 24 weeks reduced plasma high-density lipoprotein (HDL) and non-HDL cholesterol. D/D also reduced the triglyceride level. In the abdominal aorta of apoE(0) mice, these compounds significantly increased endothelial nitric oxide (NO)-mediated vasorelaxations induced by acetylcholine, but had a minor effect on relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine. Isoflavone treatment for 24 weeks had no effect on the total area of atherosclerotic plaques in the whole aorta, but DeE reduced the plaque thickness in the aortic arch by 29%, although this did not reach statistical significance. The endothelial dysfunction in apoE(0) mice is associated with hyperlipidemia and increased vascular oxidative stress measured as increased superoxide production. Both isoflavones have superoxide-scavenging activities in vitro. We suggest that chronic supplementation with bioactive isoffavone metabolites may protect endothelial NO function in apoE(0) mice, through both lipid-lowering and antioxidant actions. Copyright (C) 2003 S. Karger AG, Basel.
引用
收藏
页码:276 / 284
页数:9
相关论文
共 38 条
[1]   Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys [J].
Anthony, MS ;
Clarkson, TB ;
Hughes, CL ;
Morgan, TM ;
Burke, GL .
JOURNAL OF NUTRITION, 1996, 126 (01) :43-50
[2]   Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys [J].
Anthony, MS ;
Clarkson, TB ;
Bullock, BC ;
Wagner, JD .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (11) :2524-2531
[3]   THROMBIN-INDUCED HUMAN PLATELET-AGGREGATION IS INHIBITED BY PROTEIN-TYROSINE KINASE INHIBITORS, ST638 AND GENISTEIN [J].
ASAHI, M ;
YANAGI, S ;
OHTA, S ;
INAZU, T ;
SAKAI, K ;
TAKEUCHI, F ;
TANIGUCHI, T ;
YAMAMURA, H .
FEBS LETTERS, 1992, 309 (01) :10-14
[4]  
Baber R J, 1999, Climacteric, V2, P85, DOI 10.3109/13697139909025571
[5]   Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women [J].
Baum, JA ;
Teng, HY ;
Erdman, JW ;
Weigel, RM ;
Klein, BP ;
Persky, VW ;
Freels, S ;
Surya, P ;
Bakhit, RM ;
Ramos, E ;
Shay, NF ;
Potter, SM .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1998, 68 (03) :545-551
[6]   Antiatherosclerotic activity of drugs in relation to nitric oxide function [J].
Bult, H ;
Herman, AG ;
Matthys, KE .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 375 (1-3) :157-176
[7]   The vascular activity of some isoflavone metabolites: implications for a cardioprotective role [J].
Chin-Dusting, JPF ;
Fisher, LJ ;
Lewis, TV ;
Piekarska, A ;
Nestel, PJ ;
Husband, A .
BRITISH JOURNAL OF PHARMACOLOGY, 2001, 133 (04) :595-605
[8]   Phytoestrogens and coronary heart disease [J].
Clarkson, TB ;
Anthony, MS .
BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM, 1998, 12 (04) :589-604
[9]   Inhibition of postmenopausal atherosclerosis progression: A comparison of the effects of conjugated equine estrogens and soy phytoestrogens [J].
Clarkson, TB ;
Anthony, MS ;
Morgan, TM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (01) :41-47
[10]   The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism [J].
Clifton-Bligh, PB ;
Baber, RJ ;
Fulcher, GR ;
Nery, ML ;
Moreton, T .
MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, 2001, 8 (04) :259-265