Isoflavones are phytoestrogens known by their anti-inflammatory, antioxidant and immunomodulatory properties. Presently, there is no information on whether afrormosin, an isoflavone from Amburana cearensis A.C. Smith (Fabaceae), has some effect on the inflammatory response from stimulated human neutrophils. Thus, the aim of this study was to evaluate the antiinflammatory and antioxidant potentials of afrormosin on human neutrophils. Neutrophils (2.5 9 10 6 cells/mL) were incubated with afrormosin (3.35-335.2 lM) prepared from a product isolated from Amburana cearensis A.C. Smith with a 78.5% degree of purity and stimulated by the addition of cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate-13-acetate (PMA). Afrormosin inhibited the neutrophil degranulation induced by fMLP (10.47-335.2 lM) or PMA (0.33-167.6 lM), myeloperoxidase activity (3.3-335.2 lM), TNF-a secretion (16.7-335.2 lM) and the reactive oxygen species (ROS) generation (16.7-335.2 lM). On the other hand, afrormosin did not show any effect either on elastase or as a free radical scavenger. These data suggest that afrormosin modulates intermediary steps of the neutrophil ROS generation process. In addition, the modulatory effect of afrormosin on human neutrophil degranulation seems to be directed towards PMA-induced activation, indicating a potent inhibition of the protein kinase C activity. This study provided evidence, for the first time, to support the anti-inflammatory and antioxidant activities of afrormosin, creating novel insights into the pharmacological actions of this natural isoflavone.Neutrophils are the first cells that migrate into the infected tissue and provide innate immunity. The main functions of neutrophils include adherence, chemotaxis, phagocytosis and bactericidal activity [1]. Neutrophils also play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, ischaemia-reperfusion injury, atherosclerosis, chronic obstructive pulmonary disease and asthma [2]. In such diseases, the recruitment and stimulation of neutrophils with the release of several inflammatory mediators such as cytokines, reactive oxygen species (ROS) and myeloperoxidase (MPO) and the resultant oxidative stress can lead to tissue damage. Studies have shown that the inhibition of the oxidant response of neutrophils becomes a therapeutic challenge to control or modulate an excessive inflammatory response [3].Amburana cearensis (Fabaceae) is a medicinal plant popularly known as 'cumaru' and largely used in north-east Brazil for the treatment for asthma [4]. Phytochemical studies of its trunk bark allowed the isolation of several flavonoid derivatives, including isokaempferide, kaempferol and an isoflavone, afrormosin (afrormosin, 7-hydroxy-6,4′-dimethoxyisoflavone) ( fig. 1).Isoflavones are part of a large class of flavonoid compounds known to present several pharmacological activities, such as anti-cancer [5], antioxidant [6,7], anti-inflammatory [8] and vasorelaxant ones [9]. Previ...
