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Title: Bowman-Birk inhibitor and genistein among soy compounds that synergistically inhibit nitric oxide and prostaglandin E2 pathways in lipopolysaccharide-induced macrophages

Author
item DIA, VERMONT - UNIVERSITY OF ILLINOIS-UR
item Berhow, Mark
item GONZALEZ DE MEJIA, ELVIRA - UNIVERSITY OF ILLINOIS-UR

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/2008
Publication Date: 12/24/2008
Citation: Dia, V.P., Berhow, M.A., Gonzalez De Mejia, E. 2008. Bowman-Birk inhibitor and genistein among soy compounds that synergistically inhibit nitric oxide and prostaglandin E2 pathways in lipopolysaccharide-induced macrophages. Journal of Agricultural and Food Chemistry. 56(24):11707-11717.

Interpretive Summary: Inflammation has an important role in the development of chronic diseases. In this study, we evaluated the anti-inflammatory properties of eight soybean bioactive compounds using a macrophage cell model system. Soy saponins, isoflavones and peptides were tested by measuring their ability to inhibit inflammatory pathways. Of the eight soy bioactive compounds tested, several showed key model anti-inflammatory activities in the model studies. For the first time, synergistic interactions were observed between a peptide and an isoflavone, while an antagonistic interaction was observed between two saponins. These findings demonstrated that some key soy compounds possess anti-inflammatory properties and, therefore, are important in modulating mammalian inflammation pathways which may lead to inhibition of some types of chronic disease. Furthermore, through their interaction, they can modulate the inflammatory process. This research is leading to an understanding of what components in soy foods can be used to aid in the prevention of cancer.

Technical Abstract: Inflammation has an important role in the development of chronic diseases. In this study, we evaluated the anti-inflammatory properties of eight soybean bioactive compounds using lipopolysaccharide-induced RAW 264.7 macrophages. Genistein, daidzein, mix isoflavone glucosides, saponin A group glycosides, saponin B group glycosides, sapogenol B, Bowman-Birk inhibitor (BBI), lunasin, and pepsin-pancreatin glycinin hydrolysates were tested by measuring their ability to inhibit COX-2/PGE2 and iNOS/NO inflammatory pathways. Of the eight soy bioactive compounds (SBC) tested, BBI and sapogenol B resulted in the highest inhibition of pro-inflammatory responses at a concentration 10 times lower than the one used for the other compounds. Also, sapogenol B and genistein (molar ratio 1:1) synergistically inhibited NO and additively inhibited PGE2. Saponin A group glycosides showed inhibition of iNOS/NO pathway only, while pepsin-pancreatin glycinin hydrolysates enhanced induction and production of the four inflammatory responses. For the first time, synergistic interactions were observed between BBI and genistein inhibiting NO (92.7%) and PGE2 (95.6%) production. An antagonistic interaction was observed between saponin B and sapogenol B. All interactions were further confirmed by isobolographic analysis. These findings demonstrated that some SBC possess anti-inflammatory properties and, therefore, are important in modulating mammalian inflammation pathways which may lead to inhibition of some types of chronic disease. Furthermore, through their interaction they can modulate the inflammatory process.