Antiplatelet activity of carnosol is mediated by the inhibition of TXA2 receptor and cytosolic calcium mobilization

Carnosol, a naturally occurring phenolic diterpene found in rosemary, has been reported to exhibit antioxidant, anticancer and hepatoprotective effects. In the present study, the antiplatelet activity of carnosol was investigated. Carnosol concentration-dependently inhibited washed rabbit platelet aggregation induced by collagen and arachidonic acid (AA), with IC(50) values of 5.5+/-0.3 and 42.5+/-0.9 microM, respectively, while failed to inhibit that induced by, ADP and thrombin. Consist with inhibition of collagen-induced platelet aggregation, carnosol revealed blocking of collagen-mediated cytosolic calcium mobilization, serotonin secretion and arachidonic acid liberation. However, contrary to the inhibition of AA-induced platelet aggregation, carnosol has no effect on AA-mediated TXA(2) and PGD(2) formation, indicating carnosol may directly inhibit TXA(2) receptor, which was supported by the finding that carnosol potently inhibited U46619 (a TXA(2) mimic)-induced platelet aggregation, with an IC(50) value of 22.0+/-2.5 microM. In addition, the U46619-induced concentration-response curve was downward shifted by the application of carnosol at concentrations of 22 and 50 microM, indicating a typical non-competitive antagonism on TXA(2) receptor. Taken together, these results suggest that antiplatelet activity of carnosol may be mediated by the inhibition of TXA(2) receptor and cytosolic calcium mobilization, and carnosol has a potential to be developed as a novel-antiplatelet agent.