Protective effect of hydroxysafflor yellow A on renal ischemia‑reperfusion injury by targeting the Akt‑Nrf2 axis in mice

Abstract

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Hydroxysafflor yellow A (HSYA), a natural compound isolated from <em>Carthamus tinctorius L.</em>, has been found to possess anti‑inflammatory and antioxidant properties. However, the protective effects and potential mechanism of HSYA on I/R‑induced AKI remains unclear. In the present study, the <em>in vitro</em> hypoxia/reoxygenation (H/R) and <em>in vivo</em> renal I/R models were employed to investigate the renal protective effects and molecular mechanisms of HSYA on I/R‑induced AKI. The present results indicated that HSYA pretreatment significantly ameliorated renal damage and dysfunction in the I/R injury mice via enhancing the antioxidant capacity and suppressing the oxidative stress injury, inflammatory response, and apoptosis. Mechanistic studies showed that HSYA could upregulate Akt/GSK‑3β/Fyn‑Nrf2 axis‑mediated antioxidant gene expression both <em>in vitro</em> and <em>in vivo</em>. Moreover, HSYA‑mediated improvement in antioxidant, anti‑inflammatory, and anti‑apoptotic effects in H/R‑treated HK‑2 cells was abrogated by Akt inhibitor LY294002 supplementation. In summary, the present results demonstrated that HSYA attenuated kidney oxidative stress, inflammation response, and apoptosis induced by I/R, at least in part, via activating the Akt/GSK‑3β/Fyn‑Nrf2 axis pathway. These findings provided evidence that HSYA may be applied as a potential therapeutic agent in the treatment of I/R induced AKI.