The present study was undertaken to investigate the effects of Moutan Cortex Radicis extracts and paeonol, a major component, on rabbit platelet aggregation and thromboxane (TX) B₂ formation. Moutan Cortex Radicis methanol and butanol layers (100 μg/mL) showed the weak inhibitions, and water layer (100 μg/ mL) had no effect on the collagen-induced platelet aggregation. Whereas, hexane and EtOAc layers potently inhibited the collagen (3 μg/mL)-induced platelet aggregation with the IC_(50) values of 10.9±1.0 and 31.5±0.8 μg/mL, respectively. Paeonol isolated from the hexane-acetone layer specifically inhibited the collagen-induced platelet aggregation with the IC_(50) value of 113.1 ± 0.9 μM, whereas it had little effects on the other agonists such as AA-, thrombin-, A23187- and thapsigargin-induced platelet aggregations. Paeonol also potently inhibited the collagen-induced TXB₂ formation in rabbit platelet in a concentration-dependent manner. These results suggest that paeonol may inhibit rabbit platelet aggregation by interfering with an essential step in collagen-induced platelet activation and TXA₂ formation. Paeonol may be a promising candidate for an antiplatelet agent.

We investigated the antiplatelet effect of a newly synthesized guanidine derivative KR-32558, a sodium-hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mechanisms of action. KR-32558 concentration -dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 μg/ml) with an IC_(50) value of 85.9 μM, but with much weaker potency against aggregation induced by thapsigargin (0.5 μM) or A23187 (5 μM). And had no effect on platelet aggregation induced by arachidonic acid (100 μM), thrombin (0.05 U/ml) and U46619 (1 μM) up to 100 μM. KR-32558 completely inhibited the [Ca^(2+)] mobilization induced by collagen at concentration of 100μiM. Taken together, these observations suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.