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

• Published in: Biochemical pharmacology Vol. 58; no. 7; pp. 1167 - 1172
• Main Authors: SHAH, B. H, NAWAZ, Z, PERTANI, S. A, ROOMI, A, MAHMOOD, H, SAEED, S. A, GILANI, A. H
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01-10-1999
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arachidonic Acid - pharmacology; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Calcium - metabolism; Curcuma; Curcumin - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Drug Interactions; Humans; Medical sciences; Pharmacology. Drug treatments; Plant Extracts - chemistry; Platelet Activating Factor - pharmacology; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Signal Transduction - drug effects; Spices; Thromboxanes - biosynthesis; Human; Prostaglandin-endoperoxide synthase; Agonist; Enzyme; Thromboxane A2; Arachidonic acid; Metabolism; In vitro; Biological activity; Platelet activating factor; Antiplatelet agent; Platelet; Plant origin; Curcumin; Oxidoreductases; Mechanism of action; Food; Calcium Cations
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/s0006-2952(99)00206-3

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 microM), ADP (4 microM), platelet-activating factor (PAF; 800 nM), collagen (20 microg/mL), and arachidonic acid (AA: 0.75 mM). Curcumin preferentially inhibited PAF- and AA-induced aggregation (IC50; 25-20 microM), whereas much higher concentrations of curcumin were required to inhibit aggregation induced by other platelet agonists. Pretreatment of platelets with curcumin resulted in inhibition of platelet aggregation induced by calcium ionophore A-23187 (IC50; 100 microM), but curcumin up to 250 microM had no inhibitory effect on aggregation induced by the protein kinase C (PKC) activator phorbol myrsitate acetate (1 microM). Curcumin (100 microM) inhibited the A-23187-induced mobilization of intracellular Ca2+ as determined by using fura-2 acetoxymethyl ester. Curcumin also inhibited the formation of thromboxane A2 (TXA2) by platelets (IC50; 70 microM). These results suggest that the curcumin-mediated preferential inhibition of PAF- and AA-induced platelet aggregation involves inhibitory effects on TXA2 synthesis and Ca2+ signaling, but without the involvement of PKC.