IDB-1031

The novel flavonoid compound 3'-hydroxyfarrerol (IdB 1031) was tested in a number of in vitro experiments in order to ascertain its effects on some functions and products of human phagocytes. We found that IdB 1031 did not depress neutrophil phagocytosis and chemotaxis, whereas at a concentration of 10(-4) M it significantly (p < 0.05) reduced the fMLP-triggered neutrophil production of superoxide anion. At the same concentration, the compound decreased the release of neutrophil elastase and myeloperoxidase from neutrophils (p < 0.05). We also found evidence that IdB 1031 is a non competitive, reversible inhibitor of human neutrophil elastase (Ki 200 microns). Finally, IdB 1031 at the concentration of 10(-5) M significantly reduced the release of tumor necrosis factor-alpha and interleukin-8 from monocytes (p < 0.05). We conclude that, in spite of the moderate activity displayed by IdB 1031, these findings add to our current knowledge on the spectrum of the antiinflammatory activities of flavonoids.

The (+/-)-3'-hydroxyfarrerol (IdB 1031) is a new drug endowed with an interesting mucokinetic activity. In this study the effectiveness of IdB 1031 has been verified in a model of airway hyperreactivity and lung inflammation induced in anaesthetized guinea pig by active cigarette smoke exposure. IdB 1031 (500 mg/kg per os) completely inhibited the capacity of cigarette smoke to induce airway hyperreactivity. IdB 1031 also inhibited the recruitment of proinflammatory cells within the airway lumen as showed in bronchoalveolar lavage fluids. In line with these experiments IdB 1031 inhibited 5-lipoxygenase with an IC50 of 7.36 x 10(-6) M in human leukocytes challenged by A-23187 (2 microM). A significant reduction of the above parameters was observed also in animals exposed to smoke after repeated treatment with IdB 1031 at 200 mg/kg per os for 15 days. These results show that IdB 1031 is a promising drug with a favourable spectrum of activities on the respiratory tract.