Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling

Curcumin, a dietary spice from turmeric, is known to be anti-inflammatory, anticarcinogenic, and antithrombotic. Here, we studied the mechanism of the antiplatelet action of curcumin. We show that curcumin inhibited platelet aggregation mediated by the platelet agonists epinephrine (200 mu M) ADP (4 mu M), platelet-activating factor (PAF; 800 nM), collagen (20 mu g/mL), an d arachidonic acid (AA: 0.75 mM). Curcumin preferentially inhibited PAF- an d AA-induced aggregation (IC50; 25-20 mu M), whereas much higher concentrat ions of curcumin were required to inhibit aggregation induced by other plat elet agonists. Pretreatment of platelets with curcumin resulted in inhibiti on of platelet aggregation induced by calcium ionophore A-23187 (Ic(50); 10 0 mu M), but curcumin up to 250 mu M had no inhibitory effect on aggregatio n induced by the protein kinase C (PKC) activator phorbol myrsitate acetate (1 mu M). Curcumin (100 mu M) inhibited the A-23187-induced mobilization o f intracellular Ca2+ as determined by using fura-2 acetoxymethyl ester. Cur cumin also inhibited the formation of thromboxane A(2) (TXA(2)) by platelet s (IC50; 70 mu M) These results suggest that the curcumin mediated preferen tial inhibition of PAF- and AA-induced platelet aggregation involves inhibi tory effects on TXA(2) synthesis and Ca2+ signaling, but without the involv ement of PKC. (C) 1999 Elsevier Science Inc.