RESUMO
The water extract of Biota orientalis showed a potent inhibitory effect on platelet activating factor (PAF) binding to rabbit platelets using [3H]PAF as a ligand in our previous screening studies for Korean medicinal antagonists by the activity-guided purification studies. Another active compound, compound 1 (IC50 = 2.3 x 10(-5) M, 7.48 +/- 2.11 micrograms/ml, n = 4) was isolated from the title plant. The chemical structure of compound 1 was elucidated as pinusolidic acid by chemical and spectrometric analyses.
Assuntos
Benzofuranos/farmacologia , Naftalenos/farmacologia , Plantas Medicinais/química , Fator de Ativação de Plaquetas/antagonistas & inibidores , Animais , Benzofuranos/química , Benzofuranos/isolamento & purificação , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Técnicas In Vitro , Estrutura Molecular , Naftalenos/química , Naftalenos/isolamento & purificação , Fator de Ativação de Plaquetas/metabolismo , Coelhos , Relação Estrutura-AtividadeRESUMO
The water extract of Biota orientalis showed a potent inhibitory effect on platelet activating factor (PAF) binding to rabbit platelets using [ (3)H]PAF as a ligand in our previous screening studies for Korean medicinal antagonists by the activity-guided purification studies. Another active compound, compound 1 (IC (50) = 2.3 x 10 (-5)M, 7.48 +/- 2.11 microg/ml, n = 4) was isolated from the title plant. The chemical structure of compound 1 was elucidated as pinusolidic acid by chemical and spectrometric analyses.
RESUMO
Pinusolide, a potent platelet activating factor (PAF) receptor binding antagonist, inhibited PAF-induced aggregation of rabbit platelets with an IC50 value of 5 microM, whereas no inhibitory effects on the aggregation induced by ADP, thrombin, and collagen were observed. Pinusolide protected the mice from PAF-induced lethality with ED50 values of 1.1 mg/kg, i.v. and 69 mg/kg, p.o. Topically given pinusolide at 2 mg/ear effectively inhibited croton oil induced mouse ear edema. All the pinusolide treated ears recovered to normal healthy appearance in a sharp contrast to totally necrotized untreated ears. These results indicated that pinusolide is a potent and specific PAF antagonist in all experimental models as shown in vitro, in vivo, and in animal tests.
Assuntos
Diterpenos/farmacologia , Fator de Ativação de Plaquetas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , CoelhosRESUMO
The leaf extract of Biota orientalis showed potent PAF receptor binding antagonistic activity in our previous screening studies on 234 Korean medicinal plants using rabbit platelet receptor binding tests. The activity-guided purification of the plant extract resulted in the isolation of six compounds, including two active substances. The chemical structures of the compounds isolated were established by chemical and spectrometric analyses as dotriacontane, totarol, 8 beta-hydroxy-3-oxopimar-15-ene, cedrol (IC50 = 1.3 x 10(-5) M), pinusolide (IC50 = 2.52 x 10(-7) M), and 5-hydroxy-7,4'-dimethoxyflavone.