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Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function

Published online by Cambridge University Press:  09 March 2007

Nicole Gottstein ,
Benjamin A. Ewins ,
Clair Eccleston ,
Gary P. Hubbard ,
Ian C. Kavanagh ,
Anne-Marie Minihane ,
Peter D. Weinberg  and
Gerald Rimbach
Nicole Gottstein
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Benjamin A. Ewins
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Clair Eccleston
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Gary P. Hubbard
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Ian C. Kavanagh
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Anne-Marie Minihane
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
Peter D. Weinberg
Affiliation:
School of Animal and Microbial Sciences, The University of Reading, Reading, UK
Gerald Rimbach*
Affiliation:
Hugh Sinclair Human Nutrition Unit, School of Food Biosciences, University of Reading, UK
*
*Corresponding Author: Dr Gerald Rimbach, fax +44 118 931 0080, email G.H.Rimbach@reading.ac.uk
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Abstract

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There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the present in vitro studies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264·7) activated with interferon γ plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor α (TNF-α) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-α in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the current in vitro studies are relevant to the aetiology of coronary artery disease in vivo.

Keywords

GenisteinDaidzeinPlatelet aggregationArteriosclerosis

Information

Type
Research Article
Information
British Journal of Nutrition , Volume 89 , Issue 5 , May 2003 , pp. 607 - 615
Copyright
Copyright © The Nutrition Society 2003

References

Adlercreutz, H, Hamalainen, E & Gorbach, S (1993) Dietary phyto-oestrogens and the menopause in Japan. Lancet 342 1209–1210.Google Scholar
Arora, A, Nair, MG & Strasburg, GM (1998) Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Archives of Biochemistry and Biophysics 356 133–141.CrossRefGoogle Scholar
Arteel, GE, Briviba, K & Sies, H (1999) Protection against peroxynitrite by cocoa polyphenol oligomers. FEBS Letters 445 226–230.CrossRefGoogle Scholar
Azumi, S, Tanimura, A & Tanamoto, K (1997) A novel inhibitor of bacterial endotoxin derived from cinnamon bark. Biochemical and Biophysical Research Communications 234 506–510.CrossRefGoogle ScholarPubMed
Baker, CS, Hall, RJ, Evans, TJ, Pomerance, A, Maclouf, J, Creminon, C, Yacoub, MH & Polak, JM (1999) Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arteriosclerosis Thrombosis and Vascular Biology 19 646–655.CrossRefGoogle ScholarPubMed
Barnes, S (1995) Effect of genistein on in vitro and in vivo models of cancer. Journal of Nutrition 125 777S–783S.Google ScholarPubMed
Beckman, JS & Koppenol, WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. American Journal of Physiology 271 C1424–C1437.Google Scholar
Beretz, A, Cazenave, JP & Anton, R (1982) Inhibition of aggregation and secretion of human platelets by quercetin and other flavonoids: structure-activity relationships. Agents Actions 12 382–387.Google Scholar
Boring, L, Gosling, J, Cleary, M & Charo, IF (1998) Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394 894–897.CrossRefGoogle ScholarPubMed
Chomczynski, P & Sacchi, N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Annals of Biochemistry 162 156–159.CrossRefGoogle ScholarPubMed
Duffy, SJ, Vita, JA, Holbrook, M, Swerdloff, PL & Keaney, JF (2001) Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arteriosclerosis Thrombosis and Vascular Biology 21 1084–1089.CrossRefGoogle ScholarPubMed
Gibbons, GH & Dzau, VJ (1996) Molecular Therapies For Vascular Diseases. Science 272 689–693.Google Scholar
Guo, Q, Rimbach, G, Moini, H, Weber, S & Packer, L (2002) ESR and cell culture studies on free radical-scavenging and antioxidant activities of isoflavonoids. Toxicology 179 171–180.Google Scholar
Holder, CL, Church well, MI & Doerge, DR (1999) Quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS. Journal of Agricultural and Food Chemistry 47 3764–3770.Google Scholar
Ignarro, LJ (1994) Regulation of cytosolic guanylyl cyclase by porphyrins and metalloporphyrins. Advances in Pharmacology 26 35–65.Google Scholar
Iuliano, L, Pedersen, JZ, Pratico, D, Rotilio, G & Violi, F (1994) Role of hydroxyl radicals in the activation of human platelets. European Journal of Biochemistry 221 695–704.Google Scholar
Kapiotis, S, Herrmann, N, Held, I, Seelos, C, Ehringer, H & Gmeiner, BMK (1997) Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arteriosclerosis Thrombosis and Vascular Biology 17 2868–2874.CrossRefGoogle ScholarPubMed
Kerry, N & Abbey, M (1998) The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro. Atherosclerosis 140 341–347.Google Scholar
Kowala, MC, Recce, R, Beyer, S, Gu, C & Valentine, M (2000) Characterization of atherosclerosis in LDL receptor knockout mice: macrophage accumulation correlates with rapid and sustained expression of aortic MCP-1/JE. Atherosclerosis 149 323–330.Google Scholar
Landolfi, R, Mower, RL & Steiner, M (1984) Modification of platelet function and arachidonic acid metabolism by bioflavonoids. Structure-activity relations. Biochemical Pharmacology 33 1525–1530.CrossRefGoogle ScholarPubMed
Mitchell, JA, Larkin, S & Williams, TJ (1995) Cyclooxygenase-2: regulation and relevance in inflammation. Biochemical Pharmacology 50 1535–1542.Google Scholar
Moncada, S, Palmer, RM & Higgs, EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Revues 43 109–142.Google Scholar
Nagata, C, Takatsuko, N, Kurisu, Y & Shimizu, H (1998) Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women. Journal of Nutrition 128 209–213.CrossRefGoogle ScholarPubMed
Nakashima, S, Koike, T & Nozawa, Y (1991) Genistein, a protein tyrosine kinase inhibitor, inhibits thromboxane A2-mediated human platelet responses. Molecular Pharmacology 39 475–480.Google Scholar
Narumi, S, Finke, JH & Hamilton, TA (1990) Interferon gamma and interleukin 2 synergize to induce selective monokine expression in murine peritoneal macrophages. Journal of Biological Chemistry 265 7036–7041.CrossRefGoogle ScholarPubMed
Nelken, NA, Coughlin, SR, Gordon, D & Wilcox, JN (1991) Monocyte chemoattractant protein-1 in human atheromatous plaques. Journal of Clinical Investigation 88 1121–1127.CrossRefGoogle ScholarPubMed
Packham, MA & Mustard, JF (1977) Clinical pharmacology of platelets. Blood 50 555–573.CrossRefGoogle ScholarPubMed
Park, YC, Rimbach, G, Saliou, C, Valacchi, G & Packer, L (2000) Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappa B-dependent gene expression in RAW 264·7 macrophages. FEBS Letters 465 93–97.Google Scholar
Peluso, MR, Winters, TA, Shanahan, MF & Banz, WJ (2000) A cooperative interaction between soy protein and its isoflavone-enriched fraction lowers hepatic lipids in male obese Zucker rats and reduces blood platelet sensitivity in male Sprague-Dawley rats. Journal of Nutrition 130 2333–2342.Google Scholar
Pignatelli, P, Pulcinelli, FM, Lenti, L, Gazzaniga, PP & Violi, F (1998) Hydrogen peroxide is involved in collagen-induced platelet activation. Blood 91 484–490.CrossRefGoogle ScholarPubMed
Poole, AW & Watson, SP (1995) Regulation of cytosolic calcium by collagen in single human platelets. British Journal of Pharmacology 115 101–106.Google Scholar
Rimbach, G, Park, YP, Guo, Q, Moini, H, Saliou, C, Takayama, K, Virgili, F, Qureshi, F & Packer, L (2000 a) Nitric oxide synthesis and TNF-alpha secretion in RAW 264·7 macrophages: Mode of action of a fermented papaya preparation. Life Sciences 67 679–694.Google Scholar
Rimbach, G, Saliou, C, Canali, R & Virgili, F (2001) Interaction between cultured endothelial cells and macrophages: in vitro model for studying flavonoids in redox-dependent gene expression. Methods in Enzymology 335 238–242.Google Scholar
Rimbach, G, Valacchi, G, Canali, R & Virgili, F (2000 b) Macrophages stimulated with IFN-gamma activate NF-kB and induce MCP-1 gene expression in primary human endothelial cells. Molecular and Cell Biology Research Communications 3 238–242.Google Scholar
Ruiz-Larrea, MB, Mohan, AR, Paganga, G, Miller, NJ, Bolwell, GP & Rice-Evans, CA (1997) Antioxidant activity of phytoestrogenic isoflavones. Free Radical Research 26 63–70.Google Scholar
Setchell, KDR & Cassidy, A (1999) Dietary isoflavones: biological effects and relevance to human health. Journal of Nutrition 129 758S–767S.Google Scholar
Sheu, F, Lai, HH & Yen, GC (2001) Suppression effect of soy isoflavones on nitric oxide production in RAW 264·7 macrophages. Journal of Agricultural and Food Chemistry 49 1767–1772.CrossRefGoogle ScholarPubMed
Stuehr, DJ & Marletta, MA (1987) Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma. Journal of Immunology 139 518–525.CrossRefGoogle ScholarPubMed
Tedesco, F, Fischetti, F, Pausa, M, Dobrina, A, Sim, RB & Daha, MR (1999) Complement-endothelial cell interactions: pathophysiological implications. Molecular Immunology 36 261–268.CrossRefGoogle ScholarPubMed
Valacchi, G, Rimbach, G, Saliou, C, Weber, SU & Packer, L (2001) Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1 alpha gene expression in human keratinocytes. Toxicology 165 225–234.Google Scholar
Vitolins, MZ, Anthony, M & Burke, GL (2001) Soy protein isoflavones, lipids and arterial disease. Current Opinions in Lipidology 12 433–437.Google Scholar
Wang, Y, Rangan, GK, Goodwin, B, Tay, YC & Harris, DC (2000) Lipopolysaccharide-induced MCP-1 gene expression in rat tubular epithelial cells is nuclear factor-kappa B dependent. Kidney International 57 2011–2022.Google Scholar
Wei, H, Bowen, R, Cai, Q, Barnes, S & Wang, Y (1995) Antioxidant and anti-promotional effects of the soybean isoflavone genistein. Proceedings of the Society of Experimental Biology 208 124–130.Google Scholar
Wiseman, H, O'Reily, JD, Adlercreutz, H, Mallet, AI, Bowey, EA, Rowland, IR & Sanders, TA (2000) Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation. American Journal of Clinical Nutrition 72 395–400.CrossRefGoogle ScholarPubMed
Ylä-Herttuala, S, Lipton, BA, Rosenfeld, ME, Särkioja, T, Yoshimura, T, Leonard, EJ, Witztum, JL & Steinberg, D (1991) Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proceedings of the National Academy of Sciences, USA 88 5252–5256.Google Scholar