Abstract
Avicine pseudocyanide, a derivative of avicine isolated from Zanthoxylum integrifoliolum Men., inhibited collagen-induced platelet aggregation and release reaction in a concentration-dependent manner. Trimucytin is a collagen-like snake venom protein isolated from Trimeresurus mucrosquamatus. Avicine pseudocyanide also inhibited trimucytin (1 μg/mL)-induced platelet aggregation and release reaction concentration dependently. The ic 50 values of avicine pseudocyanide on collagen (10 μg/mL)-and trimucytin (1 μg/mL)-induced platelet aggregation were 47.3 ± 4.1 and 62.5 ± 5.6 μM, respectively. Avicine pseudocyanide at a concentration of 300 μM inhibited less than 30% of platelet aggregation induced by ADP (20 μM), AA (100 μM), U46619 (1 μM), PAF (2 ng/mL) and thrombin (0.1 U/mL). The concentration-response curve of collagen-induced platelet aggregation was shifted to the right by avicine pseudocyanide (20–100 μM) concentration dependently. The Schild plot showed that pA 2 and pA 10 values of avicine pseudocyanide were 4.8 and 4.3, respectively, with slope of −1.9. Avicine pseudocyanide also inhibited collagen (10 μg/mL)-induced aggregation of rabbit whole blood with an ic 50 of 145 ± 13 μM. Collagen-induced thromboxane B 2 formation was also inhibited by avicine pseudocyanide in a concentration-dependent manner with a maximal effect at 100 μM. However, arachidonic acid (AA)-induced thromboxane B 2 and prostaglandin D 2 formations were only partially suppressed by a high concentration of avicine pseudocyanide (300 μM). Avicine pseudocyanide (100 μM) inhibited the [ 3H]inositol monophosphate formation and the rise of intracellular Ca 2+ concentration caused by collagen but not those caused by AA, U46619, platelet-activating factor and thrombin. In the presence of prostaglandin E 1, Mg 2+-dependent platelet adhesion to collagen was inhibited by avicine pseudocyanide with an ic 50, of 278 ± 16 μM. These data indicate that avicine pseudocyanide is an inhibitor of collagen-induced platelet aggregation and platelet-collagen adhesion.
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