Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-19T03:01:29.789Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of polyphenolic compounds in the diet as inhibitors of platelet function

Published online by Cambridge University Press:  05 March 2007

Gary P. Hubbard ,
Siegfried Wolffram ,
Julie A. Lovegrove  and
Jonathan M. Gibbins
Gary P. Hubbard*
Affiliation:
School of Food Biosciences and University of Reading, Whiteknights, Reading, Berks. RG6 6AL, UK School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berks. RG6 6AL, UK
Siegfried Wolffram
Affiliation:
Institute of Animal Nutrition, Physiology and Metabolism, University of Kiel, D-24098, Kiel, Germany
Julie A. Lovegrove
Affiliation:
School of Food Biosciences and University of Reading, Whiteknights, Reading, Berks. RG6 6AL, UK
Jonathan M. Gibbins
Affiliation:
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berks. RG6 6AL, UK
*
*Corresponding author: Mr Gary Hubbard, fax +44 118931 0180, [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary components that are able to inhibit platelet function and therefore decrease the risk of cardiovascular disease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including a group of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5 d. Platelet aggregation and plasma flavonols were measured at baseline and after 5 d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P=0·001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compounds on platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.

Keywords

Dietary polyphenolsHydroxycinnamatesQuercetinPlatelet functionRisk for cardiovascular disease
Type
Micronutrient Group Symposium on ‘Micronutrient supplementation: when and why?’
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 2 , May 2003 , pp. 469 - 478
Copyright
Copyright © The Nutrition Society 2003

References

Ader, P, Wessmann, A & Wolffram, S (2000) Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radical Biology and Medicine 28, 1056–1067.Google Scholar
Aziz, AA, Edwards, CA, Lean, MEJ & Crozier, A (1998) Absorption and excretion of conjugated flavonols, including quercetin-4'-Obeta- glucoside and isorhamnetin-4'-O-beta- glucoside by human volunteers after the consumption of onions. Free Radical Research 29, 257–269.CrossRefGoogle ScholarPubMed
Beretz, A, Cazenave, JP & Anton, R (1982) Inhibition of aggregation and secretion of human-platelets by quercetin and other flavonoids–structure activity relationships. Agents and Actions 12, 382–387.CrossRefGoogle ScholarPubMed
Born, GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194, 927–929.CrossRefGoogle ScholarPubMed
Bourne, LC, Rice-Evans, CA (1998) Urinary detection of hydroxycinnamates and flavonoids in humans after high dietary intake of fruit. Free Radical Research 28, 429–438.CrossRefGoogle ScholarPubMed
Bourne, LC, Rice-Evans, CA (1999) Detecting and measuring bioavailability of phenolics and flavonoids in humans: Pharmacokinetics of urinary excretion of dietary ferulic acid. Methods in Enzymology 299, 91–106.CrossRefGoogle ScholarPubMed
Bravo, L (1998) Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutrition Reviews 56, 317–333.CrossRefGoogle ScholarPubMed
Calzada, C, Bruckdorfer, KR, Rice-Evans, CA (1997) The influence of antioxidant nutrients on platelet function in healthy volunteers. Atherosclerosis 128, 97–105.Google Scholar
Cerbone, AM, Cirillo, F, Coppola, A, Rise, P, Stragliotto, E, Galli, C, Giordano, M, Tremoli, E, Di Minno, G (1999) Persistent impairment of platelet aggregation following cessation of a short-course dietary supplementation of moderate amounts of n -3 fatty acid ethyl esters. Thrombosis and Haemostasis 82, 128–133.CrossRefGoogle ScholarPubMed
Cicmil, M, Thomas, JM, Sage, T, Barry, FA, Leduc, M, Bon, C & Gibbins, JM (2000) Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases. Journal of Biological Chemistry 275, 27339–27347.CrossRefGoogle ScholarPubMed
Clifford, MN (1999) Chlorogenic acids and other cinnamates–nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 79, 362–372.Google Scholar
Clifford, MN (2000) Chlorogenic acids and other cinnamates–nature, occurrence, dietary burden, absorption and metabolism. Journal of the Science of Food and Agriculture 80, 1033–1043.3.0.CO;2-T>CrossRefGoogle Scholar
Conquer, JA, Maiani, G, Azzini, E, Raguzzini, A & Holub, BJ (1998) Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. Journal of Nutrition 128, 593–597.CrossRefGoogle ScholarPubMed
Freedman, JE, Farhat, JH, Loscalzo, J & Keaney, JF (1996) Platelet inhibition by alpha-tocopherol is independent of its antioxidant activity. Circulation 94 4146Abstr.Google Scholar
Gibbins, JM, Briddon, S, Shutes, A, van, Vugt, MJ de, Winkel, JGJ, Saito, T Watson, SP (1998) The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin. Journal of Biological Chemistry 273, 34437–34443.Google Scholar
Gibbins, JM, Okuma, M, Farndale, R, Barnes, M & Watson, SP (1997) Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Letters 413, 255–259.CrossRefGoogle ScholarPubMed
Hertog, MGL, Feskens, EJM, Hollman, PCH, Katan, MB & Kromhout, D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease–the Zutphen Elderly Study. Lancet 342, 1007–1011.CrossRefGoogle ScholarPubMed
Hertog, MGL, Hollman, PCH & Katan, MB (1992) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. Journal of Agricultural and Food Chemistry 40, 2379–2383.Google Scholar
Hertog, MGL, Kromhout, D, Aravanis, C, Blackburn, H, Buzina, R, Fidanza, F, Giampaoli, S, Jansen, A, Menotti, A, Nedeljkovic, S, Pekkarinen, M, Simic, BS, Toshima, H, Feskens, EJM, Hollman, PCH & Katan, MB (1995) Flavonoid intake and long-term risk of coronary heart-disease and cancer in the Seven Countries Study. Archives of Internal Medicine 155, 381–386.CrossRefGoogle ScholarPubMed
Hertog, MGL, Sweetman, PM, Fehily, AM, Elwood, PC & Kromhout, D (1997) Antioxidant flavonols and ischemic heart disease in a Welsh population of men: The Caerphilly Study. American Journal of Clinical Nutrition 65, 1489–1494.Google Scholar
Hoffbrand, A & Pettit, J (1995) Essential Haematology London Blackwell Science.Google Scholar
Hollman, PCH & Arts, ICW (2000) Flavonols, flavones and flavanols–nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 80, 1081–1093.3.0.CO;2-G>CrossRefGoogle Scholar
Hollman, PCH, Bijsman, M, van, Gameren, Y, Cnossen, EPJ de, Vries, JHM Katan, MB (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radical Research 31, 569–573.Google Scholar
Hollman, PCH, vanTrijp, JMP & Buysman, M (1996) Fluorescence detection of flavonols in HPLC by postcolumn chelation with aluminum. Analytical Chemistry 68, 3511–3515.Google Scholar
Hollman, PCH, van, Trijp, JMP, Buysman, M, Van, der, Gaag, MS, Mengelers, MJB, deVries, JHM Katan, MB (1997) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Letters 418, 152–156.CrossRefGoogle ScholarPubMed
Holvoet, P & Collen, D (1994) Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB Journal 8, 1279–1284.CrossRefGoogle ScholarPubMed
Janssen, P, Mensink, RP, Cox, FJJ, Harryvan, JL, Hovenier, R, Hollman, PCH & Katan, MB (1998) Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. American Journal of Clinical Nutrition 67, 255–262.Google Scholar
Keevil, JG, Osman, HE, Reed, JD & Folts, JD (2000) Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. Journal of Nutrition 130, 53–56.CrossRefGoogle ScholarPubMed
Knekt, P, Reunanen, A, Jarvinen, R, Seppanen, R, Heliovaara, M & Aromaa, A (1994) Antioxidant vitamin intake and coronary mortality in a longitudinal population study. American Journal of Epidemiology 139, 1180–1189.CrossRefGoogle Scholar
Kroon, PA & Williamson, G (1999) Hydroxycinnamates in plants and food: current and future perspectives. Journal of the Science of Food and Agriculture 79, 355–361.3.0.CO;2-G>CrossRefGoogle 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.Google Scholar
Liu, W & Liang, NC (2000) Inhibitory effect of disodium qurecetin-7, 4'-disulfate on aggregation of pig platelets induced by thrombin and its mechanism. Acta Pharmacologica Sinica 21, 737–741.Google Scholar
McAnlis, GT, McEneny, J, Pearce, J & Young, IS (1999) Absorption and antioxidant effects of quercetin from onions, in man. European Journal of Clinical Nutrition 53, 92–96.Google Scholar
O'Reilly, JD, Sanders, TAB & Wiseman, H (2000) Flavonoids protect against oxidative damage to LDL in vitro: Use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex vivo?. Free Radical Research 33, 419–426.Google Scholar
Poole, A, Gibbins, JM, Turner, M, van, Vugt, MJ, de Winkel, JGJ, Saito, T, Tybulewicz, VLJ, Watson SP (1997) The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO Journal 16, 2333–2341.Google Scholar
Radtke, J, Linseisen, J & Wolfram, G (1998) Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Zeitschrift fur Ernahrungswissenschaft 37, 190–197.Google Scholar
Rimm, EB, Katan, MB, Ascherio, A, Stampfer, MJ & Willett, WC (1996) Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Annals of Internal Medicine 125, 384–389.Google Scholar
Russo, P, Tedesco, I, Russo, M, Russo, GL, Venezia, A & Cicala, C (2001) Effects of de-alcoholated red wine and its phenolic fractions on platelet aggregation. Nutrition Metabolism and Cardiovascular Diseases 11, 25–29.Google ScholarPubMed
Salonen, JT, Salonen, R, Seppanen, K, Rintakiikka, S, Kuukka, M, Korpela, H, Alfthan, G, Kantola, M & Schalch, W (1991) Effects of antioxidant supplementation on platelet-function–a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. American Journal of Clinical Nutrition 53, 1222–1229.Google Scholar
Serebruany, VL, Lowry, DR, Fuzailov, SY, Levine, DJ, O'Connor, CM & Gurbel, PA (2000) Moderate alcohol consumption is associated with decreased platelet activity in patients presenting with acute myocardial infarction. Journal of Thrombosis and Thrombolysis 9, 229–234.Google Scholar
Smith, JB, Selak, MA, Dangelmaier, C & Daniel, JL (1992) Cytosolic calcium as a second messenger for collagen-induced platelet responses. Biochemical Journal 288, 925–929.CrossRefGoogle ScholarPubMed
Thorogood, M (1997) Do vegetables and fruit protect against coronary heart disease? Studies among vegetarians. In Preventing Coronary Heart Disease: The Role of Antioxidants, Vegetables and Fruit: Report of an Expert Meeting 29–37 [Rogers, L, Sharp, I, editor]. London: The Stationery Office.Google Scholar
Tzeng, SH, Ko, WC, Ko, FN & Teng, CM (1991) Inhibition of platelet-aggregation by some flavonoids. Thrombosis Research 64, 91–100.Google Scholar
US Department of Agriculture (1992) The Food Pyramid Guide: A Guide to Food Choice. Home and Garden Bulletinno 252 Washington, DC: US Department of Agriculture.Google Scholar
Vinson, J (1998) Flavonoids in foods as in vitro and in vivo anti-oxidants. Flavonoids in the Living System New York: Plenum Press.Google Scholar
You, KM, Jong, HG & Kim, HP (1999) Inhibition of cyclooxy-genase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Archives of Pharmacal Research 22, 18–24.CrossRefGoogle Scholar
Zhao, XY, Gu, ZL, Attele, AS & Yuan, CS (1999) Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture. Journal of Ethnopharmacology 67, 279–285.Google Scholar