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 μM, flavone completely suppressed platelet aggregation induced by 150 μM AA in thirty-six out of forty-three subjects tested. A lower concentration (10 μM) 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 radioimmuno-assay 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.