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 μM. 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 μM. 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 μM for G3 and G4, respectively, were ∼2-fold greater than aspirin (IC max=6.0±1.0 μM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at ∼20–25 μM. 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.