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 IC₅₀ values of PJ-1 and BN52021 on PAF (2 ng/ml)-induced platelet aggregation were about 56.3 and 22.0 μM, respectively. And, the IC₅₀ value of PJ-1 toward collagen (10 μg/ml)- induced platelet aggregation was 89.4 μM. 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 B₂ formation caused by collagen, while formations of thromboxane B₂ and prostaglandin D₂ 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 [³H]PAF (3.03 ng/ml) binding to washed platelets with an IC₅₀ value of 3.9 μM. 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 A₂ in rabbit platelets.