Flavonoid inhibition of platelet procoagulant activity and phosphoinositide synthesis

Abstract

Dietary flavonoids are known for their antiplatelet activity resulting in cardiovascular protection. Phosphatidyli-nositol 4,5-bisphosphate (PIP 2) was previously reported to play a direct role in phosphatidylserine (PS) exposure, as a Ca 2+ target. Thrombin formation and platelet procoagulant activity are dependent on PS exposure. As flavonoids can inhibit phosphoinositide (PPI) kinases, we examined whether changes in PPI metabolism in flavonoid-treated platelets could be involved in their antiplatelet effects. Treatment with the flavonoids quercetin or catechin reduced PS exposure, thrombin formation, PIP 2 level and resynthesis after platelet activation with collagen, thrombin or calcium ionophore. Flavonoids also prevented [Ca 2+] j increase induced by collagen, but not by the ionophore. The ability of flavonoids to decrease PS exposure induced by ionophore treatment could result from the diminution of PIP 2 levels, whereas PS exposure induced by collagen could also be diminished by flavonoids' effects on calcium signaling dependent on PIP 2 hydrolysis. These data favor a role for PIP 2 in the antiplatelet effects of flavonoids. © 2003 International Society on Thrombosis and Haemostasis.