Roles of equol and the PI3K/Akt signaling pathway in the cardioprotective effects of enteral daidzein against ischemia-reperfusion injury in isolated rat hearts.

PURPOSE

Daidzein, a soy-derived phytoestrogen, administered directly in the heart does not show cardioprotective effects against myocardial ischemia-reperfusion (IR) in isolated rat hearts. This study aimed to investigate whether cardioprotective effects of enteral daidzein against myocardial IR are promoted by equol, a metabolite of daidzein, through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.

METHODS

Two experiments involving the Langendorff system were performed. During experiment 1, rats were divided into: daidzein group received 100 mg/kg of daidzein and control group received saline enterally 24 h before heart excision. After the rats were euthanized, blood samples were obtained to measure equol levels. Hearts were perfused with modified Krebs-Henseleit (KH) buffer before and after no-flow ischemia. During experiment 2, rats were divided into daidzein + WT (wortmannin) and control + WT groups, where daidzein (100 mg/kg) or saline (control + WT) was administered enterally 24 h before heart excision. To assess the role of the PI3K/Akt signaling pathway, an inhibitor of PI3K (wortmannin) was administered before and after no-flow ischemia in both groups. The primary outcome was the maximum left ventricular pressure derivative (LV dP/dt max) after reperfusion.

RESULTS

LV dP/dt max values of the daidzein group at 10, 15, and 20 min after reperfusion were significantly higher than those of the control group (P < 0.05). This effect was diminished by wortmannin. Enteral daidzein significantly increased serum equol levels (daidzein group: 541.5 ± 330.8 nmol/L; control group: 140.6 ± 43.3 nmol/L; P = 0.0043).

CONCLUSION

Enteral daidzein exhibited cardioprotective effects via PI3K/Akt signaling pathway activation, probably induced by increased serum equol level.