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.

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

“…None of the studies included in Table S1 tested whether the phenolic compounds target LT receptors (i.e., BLT1 and BLT2), FLAP, and/or LTC 4 hydrolase. Regarding LTA 4 hydrolase, only one study showed that isoflavones failed to inhibit (or promote) its enzymatic activity [ 143 ]. Thus, the characterization of the interaction of phenolic compounds with these elements will be essential in future studies.…”

A new method to evaluate anti-allergic effect of food component by measuring leukotriene B4 from a mouse mast cell line

“…While research on the anti-inflammatory effects of genistein has been cumulative, few studies have reported about the effect of equol on inflammation, but some physiological effects of equol such as antioxidant activity are stronger than that of genistein and daidzein (Setchell et al 2002b). Recently, Tsen et al (2016) reported that equol inhibited LTB 4 production in human neutrophils, and the activity was significantly higher than that of daidzein, suggesting the effect may be due to the inhibition of 5-LOX. Here, we showed that equol might also be a potent inhibitor of LTB 4 production by mast cells, with activity that is stronger than that of daidzein and genistein.…”

Polyphenols, vitamin C, and sugar in commercial apple beverages and their effects on antioxidant and anti-inflammatory activities in vitro

“…The cellular anti-inflammatory capacity of the apple beverage was determined by measuring the inhibition of LTB4 production and MPO activity of freshly isolated human neutrophils. Human neutrophils were isolated from the neutrophil/ erythrocyte pellet of fresh human whole blood after Ficoll-Paque gradient centrifugation and dextran sedimentation of red blood cells (Tsen et al, 2016). The whole human blood was obtained in kind from the study researchers, as such human ethics approval is not required.…”