GENISTEIN AND GUT INFLAMMATION - ROLE OF NITRIC-OXIDE

Genistein, a principal soy isoflavone, has been identified as a protei n kinase inhibitor that possesses immunosuppressive and anti-inflammat ory properties, The aim of the study was to determine if genistein mod ified chronic ileitis in guinea pigs induced by the hapten trinitroben zene sulfonic acid (TNBS), and the activity index of cultured macropha ges (RAW 264.7 cells) stimulated with lipopolysaccharide (LPS). Genist ein at low doses (0.1 mg/kg, s.c.) had mild anti-inflammatory effects in TNBS ileitis. Therapeutic benefit included a reduction in nitric ox ide production, granulocyte infiltration and improved mucosal architec ture. Genistein, at low doses, also appeared to attenuate immunohistoc hemical staining for inducible nitric oxide synthase (iNOS) and nitrot yrosine. The beneficial effects of genistein were not apparent at dose s above 0.1 mg/kg. We found that genistein also inhibited LPS-induced nitrite production by cultured macrophages and protected against LPS-i nduced necrosis despite its ability to cause apoptosis. These results indicate that genistein displayed mild antiinflammatory properties whi ch may, in part, involve an attenuation of nitric oxide release via in ducible nitric oxide synthase, and the formation of peroxynitrite.