Inhibition of lipoxygenase by soy isoflavones: Evidence of isoflavones as redox inhibitors

Hydroperoxides, the products of lipoxygenase mediated pathways, play a major role in the manifestation of chronic inflammatory diseases. Soy isoflavones act as antioxidants due to their ability to scavenge free radicals. Isoflavones inhibit the activity of soy lipoxygenase-1 and 5-lipoxygenase, from human polymorph nuclear lymphocyte in a concentration dependent manner. Spectroscopic and enzyme kinetic measurements have helped to understand the nature and mechanism of inhibition. Genistein is the most effective inhibitor of soy lipoxygenase I and 5-lipoxygenase with IC50 values of 107 and 125 mu M, respectively. Genistein and daidzein are noncompetitive inhibitors of soy lipoxygenase I with inhibition constants, K-i, of 60 and 80 mu M, respectively. Electron paramagnetic resonance and spectroscopic studies confirm that isoflavones reduce active state iron to ferrous state and prevent the activation of the resting enzyme. A model for the inhibition of lipoxygenase by isoflavones is suggested. (C) 2007 Elsevier Inc. All rights reserved.