The flavanonylflavone
morelloflavone inhibited
secretory phospholipase A2 (PLA2) in vitro, with a high potency on the human recombinant synovial and
bee venom enzymes (IC50 = 0.9 and 0.6 microM, respectively). The inhibition was apparently irreversible. In contrast, the compound was inactive on cytosolic PLA2 activity from human monocytes.
Morelloflavone scavenged
reactive oxygen species generated by human neutrophils (IC50 = 2.7 and 1.8 microM 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 ID50 = 58.5 and 74.3 micrograms/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 PLA2 with selectivity for groups II and III
enzymes and may be a pharmacological tool. In addition, it shows anti-inflammatory activity apparently not related to the synthesis of
eicosanoids, but likely dependent on other mechanisms such as scavenging of
reactive oxygen species.