PAF antagonism in vitro and in vivo by aglafoline from Aglaia elliptifolia Merr

Aglafoline, isolated from Aglaia elliptifolia Merr, inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction induced in washed rabbit platelets by PAF (platelet-activating factor). The IC₅₀ values of aglafoline, BN52021 and kadsurenone on PAF (3.6 nM)-induced platelet aggregation were about 50, 12 and 18 μM, respectively. Aglafoline also inhibited [³H]PAF (3.6 nM) binding to washed rabbit platelets with an IC₅₀ value of 17.8 ± 2.6 μM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by aglafoline with pA₂ and pA₁₀ values of 5.97 and 5.04, respectively. Although thromboxane B₂ formation caused by collagen and thrombin was partially suppressed by aglafoline, thromboxane B₂ formation caused by ionophore A23187 and arachidonic acid was not affected. Aglafoline inhibited the [³H]inositol monophosphate formation caused by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 μM). The cAMP content of washed rabbit platelets was not affected by aglafoline. Rat femoral intravenous administration of aglafoline (10 mg/kg) did not affect blood pressure. However, aglafoline (10 mg/kg) both prophylactically and therapeutically antagonized PAF (2.5 μg/kg)-induced hypotensive shock in rats. Intravenous PAF (30 ng/kg) caused severe bronchoconstriction in guinea pigs. This effect was completely blocked by aglafoline. This implies aglafoline is an effective PAF antagonist not only in vitro, but also in vivo.