alpha-Bulnesene is a sesquiterpenoid isolated from the water extract of Pogosternon cablin. It showed a potent and concentration-dependent inhibitory effect on platelet-activating factor (PAT) and arachidonic acid (AA) induced rabbit platelet aggregation. In a radioligand binding assay for the PAF receptor, alpha-bulnesene competitively inhibited [H-3]PAF binding to the PAY receptor with an IC50 value of 17.62 +/-5.68 mu M. alpha-Bulnesene also dose-dependently inhibited PAF-induced intracellular Ca2+ increase in fluo-3/AM-loaded platelets (IC50 values of 19.62 +/- 1.32 mu M). Furthermore, alpha-bulnesene inhibited AA-incluced thromboxane B-2 (TXB2) formation and prostaglandin E-2 (PGE(2)) formation. These results indicate that the inhibitory effect of alpha-bulnesene on platelet aggregation was due to a dual activity; specifically the chemical blocked PAF-induced intracellular signal transduction and interfered with cyclooxygenase activity, which resulted in a decrease in thromboxane formation. This study is the first to demonstrate that alpha-bulnesene is a PAT receptor antagonist as well as an anti-platelet aggregation agent. (c) 2006 Elsevier Inc. All rights reserved.