Liao C H, Ko F N, Wu T S, Teng C M
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
J Pharm Pharmacol. 1997 Dec;49(12):1248-53. doi: 10.1111/j.2042-7158.1997.tb06079.x.
Because platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) participates in many physiopathological responses, including inflammatory reaction, endotoxic shock, allergic diseases and platelet aggregation, PAF-receptor antagonists are important in the treatment of these diseases. A biologically active compound, bakkenolide G, extracted from the plant Petasites formosanus selectively and concentration-dependently inhibited PAF-induced platelet aggregation and ATP release. The IC50 of bakkenolide G for PAF (2 ng mL(-1))-induced platelet aggregation was 5.6 +/- 0.9 microM. Bakkenolide G also concentration-dependently inhibited PAF-induced intracellular signal transductions, including thromboxane B2 formation, and increased intra-cellular calcium concentration and phosphoinositide breakdown without affecting those caused by thrombin (0.1 units mL(-1)), collagen (10 microg mL(-1)), arachidonic acid (100 microM) and U46619 (1 microM). Bakkenolide G shifted the concentration-response curves of PAF-induced platelet aggregation parallel to the right; the Schild plot slope and the pA2 value were 1.31 +/- 0.31 and 6.21 +/- 0.75, respectively. Moreover, bakkenolide G concentration-dependently competed with [3H]PAF binding to platelets, with an IC50 value of 2.5 +/- 0.4 microM. These data strongly indicate that bakkenolide G is a specific PAF-receptor antagonist as an antiplatelet aggregatory agent.
由于血小板活化因子（PAF，1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）参与许多生理病理反应，包括炎症反应、内毒素休克、过敏性疾病和血小板聚集，因此PAF受体拮抗剂在这些疾病的治疗中具有重要意义。从台湾蜂斗菜中提取的一种生物活性化合物蜂斗菜内酯G能选择性地、浓度依赖性地抑制PAF诱导的血小板聚集和ATP释放。蜂斗菜内酯G对PAF（2 ng mL(-1)）诱导的血小板聚集的IC50为5.6±0.9 microM。蜂斗菜内酯G还能浓度依赖性地抑制PAF诱导的细胞内信号转导，包括血栓素B2的形成，并增加细胞内钙浓度和磷脂酰肌醇分解，而不影响由凝血酶（0.1单位mL(-1)）、胶原（10 microg mL(-1)）、花生四烯酸（100 microM）和U46619（1 microM）引起的这些反应。蜂斗菜内酯G使PAF诱导的血小板聚集的浓度-反应曲线平行右移；Schild图斜率和pA2值分别为1.31±0.31和6.21±0.75。此外，蜂斗菜内酯G能浓度依赖性地与[3H]PAF竞争结合血小板，并具有2.5±0.4 microM的IC50值。这些数据有力地表明，蜂斗菜内酯G作为一种抗血小板聚集剂是一种特异性PAF受体拮抗剂。
