Hispidulin, a natural flavone, and theophylline inhibited platelet aggregation triggered by adenosine-5'-monophosphate, arachidonic acid, paf-acether and collagen. Hispidulin was 100-fold more potent than theophylline. A threshold concentration of PGE1 did not modify the anti-aggregatory effect of hispidulin but potentiated the effect of theophylline. A threshold concentration of hispidulin had no effect on the inhibitory action of theophylline. Hispidulin (100 microM) and theophylline (10 mM) increased the control cAMP level in platelets 4-fold. A threshold concentration of PGE1 had a small effect on hispidulin-induced cAMP levels but increased the theophylline-induced cAMP levels 3-fold. Theophylline (10 mM)-induced cAMP levels were not modified by hispidulin. We demonstrate a correlation between the inhibition of platelet aggregation and the increase in cAMP levels induced by hispidulin. These data suggest that hispidulin could inhibit platelet aggregation by elevating cAMP levels by a mechanism different from that of theophylline or PGE1.
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