Biochemical and Molecular Actions of Nutrients Grape Seed and Grape Skin Extracts Elicit a Greater Antiplatelet Effect When Used in Combination than When Used Individually in Dogs and Humans 1 , 2

Grape products, rich in polyphenolics, inhibit platelet aggregation (PA), a risk factor for coronary artery disease. We postulated that combining extracts of grape seed (GSD) and grape skin (GSK), primary sources of grape polyphenolics, individually shown to inhibit PA, might enhance their individual antiplatelet effects. This hypothesis was examined in vitro (human platelets) and ex vivo (dog platelets) by studying the effects of the extracts on collagen-induced whole blood PA. In vitro, threshold concentration of only GSD, individually incubated with blood, significantly inhibited PA; PA was inhibited by 12.7 +/- 3.5% (P < or = 0.01). No significant changes in Pa were observed with threshold concentrations of GSK, used individually. In two dose combinations, GSD and GSK inhibited PA 40.5 +/- 10.1% (P < or = 0.005) and 96.5 +/- 3.1% (P < or = 0.001). In the ex vivo study, seven dogs were fed threshold doses of GSD or GSK individually, in combination or in combination with a proprietary enzyme blend (EB; thought to enhance bioavailability) for 8 d. PA was measured before and after each treatment. PA measurements were also repeated 24 h after the final dose of GSD + GSK + EB. Feeding the extracts individually did not affect PA, whereas feeding them in combination inhibited PA by 31.9 +/- 7.1% (P < or = 0.05). Feeding EB in addition to GSD + GSK inhibited PA by 56.2 +/- 8.1% (P < or = 0.005); 24 h later, PA was still inhibited by 31.5 +/- 10.5% (P < or = 0.05), suggesting a residual antiplatelet effect from the administration of the final dose. The results suggest that the components of GSD and GSK, when present in combination as in red wine, grape juice or in a commercial preparation containing both extracts, exhibit a greater antiplatelet effect than when present individually.

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