6533b854fe1ef96bd12adf61

RESEARCH PRODUCT

Morelloflavone, a novel biflavonoid inhibitor of human secretory phospholipase A2 with anti-inflammatory activity

subject

description

Abstract The flavanonylflavone morelloflavone inhibited secretory phospholipase A 2 (PLA 2 ) in vitro , with a high potency on the human recombinant synovial and bee venom enzymes ( IC 50 = 0.9 and 0.6 μM, respectively). The inhibition was apparently irreversible. In contrast, the compound was inactive on cytosolic PLA 2 activity from human monocytes. Morelloflavone scavenged reactive oxygen species generated by human neutrophils ( IC 50 = 2.7 and 1.8 μM for luminol and lucigenin, respectively) but did not modify cellular responses such as degranulation or eicosanoid release. This biflavonoid exerted anti-inflammatory effects in animal models, with a potent inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear inflammation in mice after topical administration. In this test, morelloflavone was found to decrease oedema and myeloperoxidase levels in ear homogenates ID 50 = 58.5 and 74.3 μg/ear, respectively). In contrast, this biflavonoid failed to modify arachidonic acid-induced ear inflammation or eicosanoid levels in ear homogenates. A significant anti-inflammatory effect was also observed in the mouse paw carrageenan edema after oral administration, with the highest inhibition at 3 hr after induction of inflammation. Morelloflavone is an inhibitor of secretory PLA 2 with selectivity for groups II and III enzymes and may be a pharmacological tool. In addition, it shows antiinflammatory activity apparently not related to the synthesis of eicosanoids, but likely dependent on other mechanisms such as scavenging of reactive oxygen species.