Select Flavonoids and Whole Juice From Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxide Release

• Published in: Circulation (New York, N.Y.) Vol. 103; no. 23; pp. 2792 - 2798
• Main Authors: Freedman, Jane E., Parker, Crawford, Li, Liqing, Perlman, Jacob A., Frei, Balz, Ivanov, Vadim, Deak, Leslie R., Iafrati, Mark D., Folts, John D.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 12.06.2001; American Heart Association, Inc
• Subjects: Adult; Antioxidants - metabolism; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Cell Line; Cell Separation; Dietary Supplements; Dose-Response Relationship, Drug; Female; Flavonoids - chemistry; Flavonoids - pharmacology; Fruit - chemistry; General and cellular metabolism. Vitamins; Humans; Male; Medical sciences; Megakaryocytes - drug effects; Megakaryocytes - enzymology; Middle Aged; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Function Tests; Protein Kinase C - metabolism; Rosales; Superoxides - metabolism; Vitamin E - blood; Aggregation; Human; Platelet; Nitric oxide; Grape; Antioxidant; Flavonoid; Fruit juice; Biological activity
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.103.23.2792

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/10 8 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). α-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.