Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Antiplatelet Action of 3', 4'-Diisovalerylkhellactone Diester Purified from Peucedanum japonicum Thunb.
George HSIAOFeng-Nien KOTing-Ting JONGChe-Ming TENG
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1998 Volume 21 Issue 7 Pages 688-692

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Abstract

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.

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