Inhibition of platelet aggregation by manoalide: preliminary results

Manoalide (MND), a sesterterpenoid first isolated from the marine sponge Luffariela variabilis and later synthesized by Japanese chemists, exhibits anti-inflammatory activity and directly inactivates bee and snake venom phospholipase A2. We investigated the effects of MND on platelet aggregation induced by PAF-acether, arachidonic acid (AA), ADP and thrombin. Rabbit platelet aggregation was inhibited by MND in a dose-dependent manner. MND also inhibited the aggregation induced by AA and ADP but not that induced by thrombin. Since this marine natural product is also a potent inhibitor of lipoxygenase in human polymorphonuclear neutrophils, MND appears to be a useful tool for determining the role of phospholipase A2 in biological processes.