(Circulation. 2001;103:2792.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Select Flavonoids and Whole Juice From Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxide Release
From the Departments of Pharmacology and Medicine, Georgetown University Medical Center, Washington, DC (J.E.F., C.P., L.L., J.A.P., L.R.D.); Linus Pauling Institute, Corvallis, Ore (B.F., V.I.); Uniformed Services University of Health Sciences, Bethesda, Md (M.D.I.); and the University of Wisconsin, Madison (J.D.F.).
Correspondence to Dr Jane E. Freedman, Med-Dent Building, Room NE 403, Georgetown University Medical Center, 3900 Reservoir Rd NW, Washington, DC 20007. E-mail freedmaj{at}gunet.georgetown.edu
Background—Moderate red wine consumption is inversely associated with coronary ischemia, and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. In this study, the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined.
Methods and
Results—Incubation of platelets with
dilute PGJ led to inhibition of aggregation, enhanced release of
platelet-derived NO, and decreased superoxide production.
To confirm the in vivo relevance of these findings, 20 healthy subjects
consumed 7 mL · kg-1 ·
d-1 of PGJ for 14 days. Platelet
aggregation was inhibited after PGJ supplementation,
platelet-derived NO production increased from 3.5±1.2 to
6.0±1.5 pmol/108 platelets, and
superoxide release decreased from 29.5±5.0 to 19.2±3.1 arbitrary
units (P<0.007 and
P<0.05, respectively).
-Tocopherol levels increased significantly after PGJ
consumption (from 15.6±0.7 to 17.6±0.9 µmol/L;
P<0.009), and the plasma
protein–independent antioxidant activity increased by 50.0%
(P<0.05). Last, incubation of
platelets with select flavonoid fractions isolated from PGJ
consistently attenuated superoxide levels but had variable
effects on whole-blood aggregation, platelet aggregation, and NO
release.
Conclusions—Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation, increase platelet-derived NO release, and decrease superoxide production. These findings may be a result of antioxidant-sparing and/or direct effects of select flavonoids found in PGJ. The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol consumption, in cardiovascular disease.
Key Words: platelets • antioxidants • nitric oxide • thrombosis • nutrition
This article has been cited by other articles:
 |
|
 |
|
  M. M. Dohadwala and J. A. Vita Grapes and Cardiovascular Disease J. Nutr., September 1, 2009; 139(9): 1788S - 1793S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Walter, N. Etienne-Selloum, D. Brasse, R. Schleiffer, V. Bekaert, P. M. Vanhoutte, A. Beretz, and V. B. Schini-Kerth Red Wine Polyphenols Prevent Acceleration of Neovascularization by Angiotensin II in the Ischemic Rat Hindlimb J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 699 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, S.-j. Zhu, D. Wang, Y.-j. Wei, and S.-S. Hu Intramyocardial injection of tannic acid attenuates postinfarction remodeling: A novel approach to stabilize the breaking extracellular matrix J. Thorac. Cardiovasc. Surg., January 1, 2009; 137(1): 216 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Churchill, M.-H. Disatnik, G. R. Budas, and D. Mochly-Rosen Ethanol for cardiac ischemia: the role of protein kinase c Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 469 - 483. [Abstract] [PDF]
|
|
|
|
|
|
P. Gresele, P. Pignatelli, G. Guglielmini, R. Carnevale, A. M. Mezzasoma, A. Ghiselli, S. Momi, and F. Violi Resveratrol, at Concentrations Attainable with Moderate Wine Consumption, Stimulates Human Platelet Nitric Oxide Production J. Nutr., September 1, 2008; 138(9): 1602 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Karatzi, C. Papamichael, E. Karatzis, T. G. Papaioannou, P. Th. Voidonikola, G. D. Vamvakou, J. Lekakis, and A. Zampelas Postprandial Improvement of Endothelial Function by Red Wine and Olive Oil Antioxidants: A Synergistic Effect of Components of the Mediterranean Diet J. Am. Coll. Nutr., August 1, 2008; 27(4): 448 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Corder Red wine, chocolate and vascular health: developing the evidence base Heart, July 1, 2008; 94(7): 821 - 823. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Castilla, A. Davalos, J. L. Teruel, F. Cerrato, M. Fernandez-Lucas, J. L. Merino, C. C. Sanchez-Martin, J. Ortuno, and M. A Lasuncion Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients Am. J. Clinical Nutrition, April 1, 2008; 87(4): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Erlund, R. Koli, G. Alfthan, J. Marniemi, P. Puukka, P. Mustonen, P. Mattila, and A. Jula Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol Am. J. Clinical Nutrition, February 1, 2008; 87(2): 323 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Anselm, M. Chataigneau, M. Ndiaye, T. Chataigneau, and V. B. Schini-Kerth Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS Cardiovasc Res, January 15, 2007; 73(2): 404 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Castilla, R. Echarri, A. Davalos, F. Cerrato, H. Ortega, J. L. Teruel, M. F. Lucas, D. Gomez-Coronado, J. Ortuno, and M. A Lasuncion Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects Am. J. Clinical Nutrition, July 1, 2006; 84(1): 252 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Davalos, C. Fernandez-Hernando, F. Cerrato, J. Martinez-Botas, D. Gomez-Coronado, C. Gomez-Cordoves, and M. A. Lasuncion Red Grape Juice Polyphenols Alter Cholesterol Homeostasis and Increase LDL-Receptor Activity in Human Cells In Vitro J. Nutr., July 1, 2006; 136(7): 1766 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pignatelli, S. Di Santo, B. Buchetti, V. Sanguigni, A. Brunelli, and F. Violi Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment FASEB J, June 1, 2006; 20(8): 1082 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Szmitko and S. Verma Antiatherogenic potential of red wine: clinician update Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2023 - H2030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Zilkens, V. Burke, J. M. Hodgson, A. Barden, L. J. Beilin, and I. B. Puddey Red Wine and Beer Elevate Blood Pressure in Normotensive Men Hypertension, May 1, 2005; 45(5): 874 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Williamson and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies Am. J. Clinical Nutrition, January 1, 2005; 81(1): 243S - 255S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A Vita Polyphenols and cardiovascular disease: effects on endothelial and platelet function Am. J. Clinical Nutrition, January 1, 2005; 81(1): 292S - 297S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L Keen, R. R Holt, P. I Oteiza, C. G Fraga, and H. H Schmitz Cocoa antioxidants and cardiovascular health Am. J. Clinical Nutrition, January 1, 2005; 81(1): 298S - 303S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sies, T. Schewe, C. Heiss, and M. Kelm Cocoa polyphenols and inflammatory mediators Am. J. Clinical Nutrition, January 1, 2005; 81(1): 304S - 312S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Albers, S. Varghese, O. Vitseva, J. A. Vita, and J. E. Freedman The Antiinflammatory Effects of Purple Grape Juice Consumption in Subjects with Stable Coronary Artery Disease Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): e179 - e180. [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Xu, K. Ikeda, and Y. Yamori Upregulation of Endothelial Nitric Oxide Synthase by Cyanidin-3-Glucoside, a Typical Anthocyanin Pigment Hypertension, August 1, 2004; 44(2): 217 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Casani, E. Segales, G. Vilahur, A. B. de Luna, and L. Badimon Moderate Daily Intake of Red Wine Inhibits Mural Thrombosis and Monocyte Tissue Factor Expression in an Experimental Porcine Model Circulation, July 27, 2004; 110(4): 460 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ralay Ranaivo, O. Rakotoarison, A. Tesse, C. Schott, A. Randriantsoa, A. Lobstein, and R. Andriantsitohaina Cedrelopsis grevei induced hypotension and improved endothelial vasodilatation through an increase of Cu/Zn SOD protein expression Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H775 - H781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Freedman High-fat diets and cardiovascular disease: Are nutritional supplements useful? J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1750 - 1752. [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Balestrieri, D. Castaldo, C. Balestrieri, L. Quagliuolo, A. Giovane, and L. Servillo Modulation by flavonoids of PAF and related phospholipids in endothelial cells during oxidative stress J. Lipid Res., February 1, 2003; 44(2): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Goldberg To Drink or Not to Drink? N. Engl. J. Med., January 9, 2003; 348(2): 163 - 164. [Full Text] [PDF]
|
|
|
|
|
|
D. J O'Byrne, S. Devaraj, S. M Grundy, and I. Jialal Comparison of the antioxidant effects of Concord grape juice flavonoids {alpha}-tocopherol on markers of oxidative stress in healthy adults Am. J. Clinical Nutrition, December 1, 2002; 76(6): 1367 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R Holt, S. A Lazarus, M C. Sullards, Q. Y. Zhu, D. D Schramm, J. F Hammerstone, C. G Fraga, H. H Schmitz, and C. L Keen Procyanidin dimer B2 [epicatechin-(4{beta}-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa Am. J. Clinical Nutrition, October 1, 2002; 76(4): 798 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Y. Zhu, R. R. Holt, S. A. Lazarus, T. J. Orozco, and C. L. Keen Inhibitory Effects of Cocoa Flavanols and Procyanidin Oligomers on Free Radical-Induced Erythrocyte Hemolysis Experimental Biology and Medicine, May 1, 2002; 227(5): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Holt, D. D. Schramm, C. L. Keen, S. A. Lazarus, and H. H. Schmitz Chocolate Consumption and Platelet Function JAMA, May 1, 2002; 287(17): 2212 - 2213. [Full Text] [PDF]
|
|
|
|
|
|
F. Violi, P. Pignatelli, F.M. Pulcinelli, J. E. Freedman, C. Parker III, L. Li, J. A. Perlman, B. Frei, V. Ivanov, L. R. Deak, et al. Synergism Among Flavonoids in Inhibiting Platelet Aggregation and H2O2 Production Response Circulation, February 26, 2002; 105 (8): e53 - e53. [Full Text] [PDF]
|
|