Rui Cao

Southeast University, China

Title: Atractylenolide I Alleviates Renal Ischemia-Reperfusion Injury Via HIF-1? /LDHA/NLRP3 Axis By Regulating Macrophage Polarization

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Biography

Rui Cao is a doctoral candidate in Urology whose research focuses on the role of macrophages in acute and chronic kidney injury. He is proficient in animal disease modeling, cell-based functional assays, and molecular target validation experiments related to renal injury

Abstract

Renal ischemia-reperfusion injury (RIRI) is a common and severe clinical renal disorder with limited therapeutic options. Atractylenolide I (ATL-I), a key bioactive component of Atractylodes macrocephala, possesses potent anti-inflammatory and organ-protective activities. Macrophage M1 pro-inflammatory polarization exacerbates RIRI progression, but whether ATL-I protects against RIRI via regulating macrophage polarization remains unclear. We investigated ATL-I's renoprotective effects in a mouse RIRI model and explored mechanisms in bone marrow-derived macrophages (BMDMs). Molecular docking and cellular thermal shift assay (CETSA) identified HIF-1? as ATL-I's direct binding target, and HIF-1? knockout confirmed its functional role. ATL-I pretreatment significantly attenuated RIRI-induced renal dysfunction and histopathological injury. It suppressed M1 macrophage polarization by directly binding HIF-1?, inhibiting its nuclear translocation and promoting degradation. HIF-1? knockdown inhibited LDHA/NLRP3 inflammasome activation, while HIF-1? stabilization abrogated ATL-I's protective effects. To our knowledge, this is the first study demonstrating that ATL-I protects against RIRI via theHIF-1?/LDHA/NLRP3 axis, providing a promising therapeutic candidate.