Alpha-bulnesene, a novel PAF receptor antagonist isolated from Pogostemon cablin.
Alpha-bulnesene is a sesquiterpenoid isolated from the water extract of Pogostemon cablin. It showed a potent and concentration-dependent inhibitory effect on platelet-activating factor (PAF) and arachidonic acid (AA) induced rabbit platelet aggregation. In a radioligand binding assay for the PAF receptor, alpha-bulnesene competitively inhibited [(3)H]PAF binding to the PAF receptor with an IC(50) value of 17.62+/-5.68microM. alpha-Bulnesene also dose-dependently inhibited PAF-induced intracellular Ca(2+) increase in fluo-3/AM-loaded platelets (IC(50) values of 19.62+/-1.32microM). Furthermore, alpha-bulnesene inhibited AA-induced thromboxane B(2) (TXB(2)) 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 PAF receptor antagonist as well as an anti-platelet aggregation agent.
Hsu
Hui-Chun
HC
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Yang
Wen-Chia
WC
Tsai
Wei-Jern
WJ
Chen
Chien-Chih
CC
Huang
Hui-Yu
HY
Tsai
Ying-Chieh
YC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010936:Plant Extracts / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013931:Thromboxanes / Q000378:metabolism
D010936:Plant Extracts; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D013931:Thromboxanes; C512113:alpha-bulnesene; C039351:platelet activating factor receptor; D016718:Arachidonic Acid; D002118:Calcium