PIPERBETOL, METHYLPIPERBETOL, PIPEROL-A AND PIPEROL-B - A NEW SERIES OF HIGHLY SPECIFIC PAF RECEPTOR ANTAGONISTS FROM PIPER BETLE

Piperbetol, methylpiperbetol, piperol A, and piperol B, isolated from Piper betle, selectively inhibited the washed rabbit platelet aggregat ion induced by platelet activating factor (PAF) in a concentration-dep endent manner. The IC50 values of piperbetol, methylpiperbetol, pipero l A, piperol B, and ginkgolide B were about 18.2, 10.6, 114.2, 11.8, a nd 4.8 mu mol/l, respectively. The inhibitory potency of ginkgolide B was about 2.8, 1.2, 22.8, and 1.4 times higher than those of piperbeto l, methylpiperbetol, piperol A, and piperol B, The concentration-respo nse curve of PAF-induced platelet aggregation was shifted to the right by 50 mu mol/l of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B. The EC50 of PAF was increased by these compounds fr om 1.5 nmol/l to 14.3, 23.1, 2.4, 20.6, and 47.2 mol/l, respectively. The compounds also inhibited the binding of [H-3]-PAF to washed rabbit platelets with IC50 values of 8.7, 5.3, 88, 6.2, and 1.8 mu mol/l. Co rrelating with the inhibitory potency for platelet aggregation, the in hibitory potency of ginkgolide B for binding of PAF was about 3.8, 1.9 , 48, and 2.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. However, the aggregation of washed rabbit p latelets induced by threshold ADP and arachidonic acid were unaffected by piperbetol, methylpiperbetol, piperol A, and piperol B. Furthermor e, piperbetol, methylpiperbetol, piperol A, and piperol B had no effec ts on the cAMP contents in rest washed rabbit platelets, In conclusion , these data indicate that piperbetol, methylpierbetol, piperol A, and piperol B are effective PAF receptor antagonists in vitro.