Piperbetol, Methylpiperbetol, Piperol A and Piperol B: A New Series of Highly Specific PAF Receptor Agonists from Piper betle

Abstract

Piperbetol, methylpiperbetol, piperol A, and piperol B, isolated from Piper betle, selectively inhibited the washed rabbit platelet aggregation induced by platelet activating factor (PAF) in a concentration-dependent manner. The IC₅₀ values of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B were about 18.2, 10.6, 114.2, 11.8, and 4.8 µmol/l, respectively. The inhibitory potency of ginkgolide B was about 2.8, 1.2, 22.8, and 1.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by 50 µmol/l of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B. The EC₅₀ of PAF was increased by these compounds from 1.5 nmol/l to 14.3, 23.1, 2.4, 20.6, and 47.2 nmol/l, respectively. The compounds also inhibited the binding of [³ H]-PAF to washed rabbit platelets with IC₅₀ values of 8.7, 5.3, 88, 6.2, and 1.8 µmol/l. Correlating with the inhibitory potency for platelet aggregation, the inhibitory 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 platelets induced by threshold ADP and arachidonic acid were unaffected by piperbetol, methylpiperbetol, piperol A, and piperol B. Furthermore, piperbetol, methylpiperbetol, piperol A, and piperol B had no effects 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.

Key words

Platelet activating factor - PAF antagonist - platelet aggregation - piperbetol - methylpiperbetol - piperol A - piperol B - Piper betle - Piperaceae