Protective effect of hydroxysafflor yellow A on renal ischemia‑reperfusion injury by targeting the Akt‑Nrf2 axis in mice
Yueming Wang, Kaiyue Han, Zile Li, Xiaoxuan Tang, Chen Wang, Yaxuan Zhao, Hengchao Zhang, Ziran Geng, Jie Kong, Xiying Luan, Yanlian Xiong
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.