Relative Inhibitions of 5-Lipoxygenase and Myeloperoxidase and Free-Radical Scavenging Activities of Daidzein, Dihydrodaidzein, and Equol.

Abstract

The effects of bioavailability and metabolic transformation on the biological activities of daidzein are relatively unknown. The effects of daidzein, dihydrodaidzein, and equol at physiologically relevant concentrations on the production of leukotriene B4 and F2-isoprostanes, and myeloperoxidase enzyme activity in freshly isolated human neutrophils were examined. Equol, at physiological concentrations, inhibited leukotriene B4 production (IC50-200 nmol/L) in human neutrophils significantly more than daidzein and dihydrodaidzein (IC50 values >1000 nmol/L). Daidzein, dihydrodaidzein, and equol did not affect the enzymatic hydrolysis of leukotriene A4 to leukotriene B4, suggesting that they exerted their inhibitory effects on the 5-lipoxygenase activity. Daidzein (IC50 = 600 nmol/L) protected against free radical peroxidation of arachidonic acid significantly more than did equol and dihydrodaidzein (IC50 values >1000 nmol/L). Equol also showed significantly greater inhibition of myeloperoxidase activity (IC50 = 450 nmol/L) when compared to daidzein and dihydrodaidzein. Equol accumulated within the human neutrophils at significantly higher concentrations than daidzein and dihydrodaidzein after incubation with the three compounds at physiologically relevant concentrations. Neutrophils were able to accumulate intracellular daidzein, dihydrodaidzein, and equol up to a concentration of ∼600 nmol/L. Our results provide in vitro evidence that the biological activities of daidzein are profoundly influenced by bioavailability and metabolic transformation.