Equol is more active than soy isoflavone itself to compete for binding to thromboxane A 2 receptor in human platelets

Abstract

Introduction Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A 2 (TxA 2) receptor. Material and methods Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA 2 receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA 2 was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA 2 mimic) and the calcium ionophore A23187. Results The data showed that aglycone isoflavones and equol bind to TxA 2 receptor in the µmol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [ 3H]-SQ29585 binding was: equol > genistein > daidzein > glycitein ≫ genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA 2 binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA 2 analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP. Conclusions The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A 2 receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.