Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s(-1)) and high (1800 s(-1)) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIb alpha deficient mice. The interaction of these soy isoflavone with 14-3-3 zeta was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of alpha IIb beta 3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s(-1)). These soy isoflavone interact with 14-3-3 zeta and inhibited both GPIb-IX and alpha IIb beta 3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3 zeta is a novel target of genistein and daidzein. 14-3-3 zeta, an adaptor protein that regulates both GPIb-IX and alpha IIb beta 3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.

Automated summary

Soy isoflavones genistein and daidzein were found to inhibit thrombosis formation, particularly under high shear force. They interact with 14-3-3ζ and suppress multiple platelet activation pathways and outside-in signaling transduction. These findings suggest that 14-3-3ζ is a novel target for genistein and daidzein in platelet inhibition.