Antiplatelet action of 3′,4′-diisovalerylkhellactone diester purified from Peucedanum japonicum Thunb.

3',4'-Diisovalerylkhellactone diester (PJ-1) is a coumarin derivative purified from the medicinal herb Peucedanum japonicum Thunb, We examined its in vitro effects on various aspects of platelet reactivity, PJ-1 inhibited the aggregation and ATP release of rabbit platelets induced by PAF (platelet-activating factor) and collagen, The IC,, values of PJ-1 and BN52021 on PAF (2 ng/ml)-induced platelet aggregation were about 56.3 and 22.0 mu M, respectively, And, the IC50 value of PJ-1 toward collagen (10 mu g/ml)-induced platelet aggregation was 89.4 mu M. Although the platelet aggregation caused by arachidonic acid and thrombin were barely inhibited by PJ-1, the release reactions were partially suppressed. PJ-1 also inhibited the thromboxane B-2 formation caused by collagen, while formations of thromboxane B-2 and prostaglandin D-2 caused by arachidonic acid were not affected. The phosphoinositide breakdown caused by PAF was inhibited by PJ-1, but those by other inducers were not affected significantly. PJ-1 inhibited the intracellular Ca2+ increase caused by PAF in fura-2-loaded platelets. PJ-1 also concentration-dependently inhibited [H-3]PAF (3.03 ng/ml) binding to washed platelets with an IC,, value of 3.9 mu M. It is concluded that the main antiplatelet effect of PJ-1 may be due to dual activities on the blockade of PAF receptor-induced activation and also the inhibition of phospholipase A(2) in rabbit platelets.