Sodium aescinate protects renal ischemia-reperfusion and pyroptosis through AKT/NLRP3 signaling pathway.

Abstract

Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal injury. Studies have shown that sodium aescinate (SA) may serve as a potential therapeutic agent, although its exact mechanism remains unclear. This study first evaluated the efficacy of SA using a mouse renal ischemia-reperfusion model. Subsequently, its mechanism was elucidated through systematic bioinformatics, and finally validated through in vitro and in vivo experiments. The results demonstrated that SA has a protective effect on renal function in mice with RIRI. Bioinformatic analysis indicated that the pyroptosis pathway is significantly activated during renal ischemia-reperfusion injury, and immunohistochemistry showed that the level of renal pyroptosis is upregulated during ischemia-reperfusion injury. Administration of SA was able to reduce the expression of pyroptosis-related proteins (GSDMD, NLRP3, IL-1β) in RIRI. In vitro and in vivo experiments further confirmed that SA exerts an anti-pyroptotic effect by inhibiting the AKT/NLRP3 signaling pathway. Ultimately, SA mitigates kidney injury in IRI mice by suppressing renal failure through inhibition of the AKT/NLRP3 signaling pathway.