title: Hispidulin, a natural flavone, inhibits human platelet aggregation by increasing cAMP levels.
abstract: 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.
authors.affiliation: INSERM U.200, Université Paris XI, Clamart, France.
authors.forename: B
authors.initials: B
authors.lastname: Bourdillat
authors.forename: D
authors.initials: D
authors.lastname: Delautier
authors.forename: C
authors.initials: C
authors.lastname: Labat
authors.forename: J
authors.initials: J
authors.lastname: Benveniste
authors.forename: P
authors.initials: P
authors.lastname: Potier
authors.forename: C
authors.initials: C
authors.lastname: Brink
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002021:Buffers; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D013806:Theophylline / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D002021:Buffers; D047309:Flavones; D005419:Flavonoids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D003094:Collagen; D013806:Theophylline; D000242:Cyclic AMP; D000527:Alprostadil; C055957:hispidulin