Inhibition of human platelet cyclic AMP phosphodiesterase and of platelet aggregation by a hemisynthetic flavonoid, amentoflavone hexaacetate.
Amentoflavone hexaacetate (AmAc) was synthesized from natural amentoflavone (Am), a biflavonoid extracted from Viburnum lantana L. Am does not inhibit aggregation of intact platelets up to a concentration of 100 microM but inhibits human platelet cAMP phosphodiesterase (IC50 = 22.0 microM). AmAc is a potent inhibitor of the aggregation of washed human platelets induced by ADP (IC50 = 2.3 microM) or collagen (IC50 = 4.7 microM). AmAc inhibits crude (IC50 = 8.6 microM) or partially purified (IC50 = 42.2 microM) human platelet cAMP phosphodiesterase. In the presence of prostaglandin E1, AmAc (10 microM) induces a 3.7-fold increase in total platelet cAMP. The characteristics of this action suggest a role for cAMP in the mechanism of action of AmAc. The incubation of AmAc with intact platelets for 5 min is necessary for its activity.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D044946:Biflavonoids; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D003094:Collagen / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*
D044946:Biflavonoids; D005419:Flavonoids; C047397:amentoflavone hexaacetate; D000244:Adenosine Diphosphate; D003094:Collagen; C011164:amentoflavone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases