Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa

In this study, rutaecarpine was tested for its antiplatelet activities in human platelet-rich plasma. In human platelet-rich plasma, rutaecarpine (40-200 μM) inhibited aggregation stimulated by a variety of agonists (i.e., collagen, ADP, adrenaline and arachidonic acid). The antiplatelet activity of rutaecarpine (120 μM) was not significantly attenuated by pretreatment with the nitric oxide synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA) (100 μM) or N(G)-nitro-L-arginine methyl ester (L-NAME) (200 μM) and with the guanylyl cyclase inhibitor methylene blue (100 μM). In addition, rutaecarpine (40-200 μM) did not significantly affect cyclic AMP and cyclic GMP levels in human washed platelets, whereas it significantly inhibited thromboxane B₂ formation stimulated by collagen (10 μg/ml) and thrombin (0.1 U/ml). Furthermore, rutaecarpine (40-200 μM) inhibited [³H]inositol monophosphate formation stimulated by collagen and thrombin in [³H]myoinositol-loaded platelets. It is concluded that the antiplatelet effects of rutaecarpine are due to inhibition of thromboxane formation and phosphoinositide breakdown.