Bakkenolide G, a natural PAF-receptor antagonist.

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.