title: Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation.
abstract: Gingerols, the active components of ginger (the rhizome of Zingiber officinale, Roscoe), represent a potential new class of platelet activation inhibitors. In this study, we examined the ability of a series of synthetic gingerols and related phenylalkanol analogues (G1-G7) to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid (AA)-induced platelet serotonin release and aggregation in vitro. The IC(50) for inhibition of AA-induced (at EC(50)=0.75 mM) serotonin release by aspirin was 23.4+/-3.6 microM. Gingerols and related analogues (G1-G7) inhibited the AA-induced platelet release reaction in a similar dose range as aspirin, with IC(50) values between 45.3 and 82.6 microM. G1-G7 were also effective inhibitors of AA-induced human platelet aggregation. Maximum inhibitory (IC(max)) values of 10.5+/-3.9 and 10.4+/-3.2 microM for G3 and G4, respectively, were approximately 2-fold greater than aspirin (IC(max)=6.0+/-1.0 microM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at approximately 20-25 microM. The mechanism underlying inhibition of the AA-induced platelet release reaction and aggregation by G1-G7 may be via an effect on cyclooxygenase (COX) activity in platelets because representative gingerols and related analogues (G3-G6) potently inhibited COX activity in rat basophilic leukemia (RBL-2H3) cells. These results provide a basis for the design of more potent synthetic gingerol analogues, with similar potencies to aspirin, as platelet activation inhibitors with potential value in cardiovascular disease.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: K L
authors.initials: KL
authors.lastname: Koo
authors.forename: A J
authors.initials: AJ
authors.lastname: Ammit
authors.forename: V H
authors.initials: VH
authors.lastname: Tran
authors.forename: C C
authors.initials: CC
authors.lastname: Duke
authors.forename: B D
authors.initials: BD
authors.lastname: Roufogalis
mesh_terms: D000328:Adult; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002396:Catechols; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D012701:Serotonin; C007845:gingerol; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin