Inhibition in vitro of platelet aggregation and arachidonic acid metabolism by flavone.
The effects of flavone on platelet aggregation and arachidonic acid (AA) metabolism were tested in vitro. When incubated at a concentration of 50 microM, flavone completely suppressed platelet aggregation induced by 150 microM AA in thirty-six out of forty-three subjects tested. A lower concentration (10 microM) was effective in about 50% of the donors. Flavone also inhibited the second wave of aggregation induced by epinephrine and ADP. Platelet thromboxane formation, estimated both by radioimmunoassay measurements and by studies of 14C-labeled AA metabolism, was depressed by flavone. Flavone-treated platelets preferentially utilized [14C]AA for the lipoxygenase pathway while cyclo-oxygenase activity was depressed. Adenosine 3':5'-cyclic monophosphate (cAMP) was measured in flavone-treated and control platelets. While their baseline levels were similar, flavone-treated platelets showed a lower stimulation of cAMP induced by prostacyclin (PGI2) than did controls. Phosphodiesterase activity was not affected by flavone as judged from the decay rates of PGI2-stimulated cAMP levels. From these findings we conclude that the antiaggregating activity of flavone is not a consequence of changes in platelet cAMP but is due to inhibition of cyclo-oxygenase.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects*
D001095:Arachidonic Acids; D005419:Flavonoids; D016718:Arachidonic Acid; D000242:Cyclic AMP