Cardioprotective effects of S-equol and role of the PI3K/Akt pathway in the isolated ischemic rat heart

Purpose: This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium in an isolated rat heart model. Additionally, we examined the role of the PI3K/Akt signaling pathway.l Methods Rat hearts were perfused using the Langendorff system and assigned to receive 1) modified Krebs–Henseleit (KH) buffer containing 1 µmol/L S-equol (EQ), 2) KH buffer (Cont), 3) KH buffer supplemented with 1 µmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW), or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min prior to no-flow ischemia for 7.5 min, followed by reperfusion for 20 min. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting. Results The LV dP/dt max in the EQ group was greater than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β in the EQ group compared to the Cont group. However, these effects were not observed in the presence of wortmannin. Conclusion S-equol exerted a protective effect against myocardial ischemia-reperfusion injury, possibly by activating PI3K/Akt signaling.