Lycium barbarum Polysaccharide Alleviates Renal Damage in Mouse Sepsis by Regulating M1 / M2 Macrophage Polarization

ABSTRACT Lycium barbarum polysaccharide (LBP), a compound derived from the traditional Chinese herb Lycium barbarum , has been recognized for its immunomodulatory and anti‐inflammatory properties. Sepsis‐associated acute kidney injury (SA‐AKI) is characterized by systemic inflammation and organ dysfunction. Given the critical role of dysregulated M1/M2 macrophage polarization in the pathogenesis of SA‐AKI, this study investigated the potential protective effects of LBP both in vivo and in vitro. In the mice model of SA‐AKI induced by colonic ligation puncture, LBP administration significantly reduced biochemical indicators of renal injury, including BUN, creatinine, KIM‐1, and NGAL. At the molecular level, LBP decreased the expression of M1 macrophage markers such as iNOS while elevating M2 markers like Arg‐1. Consistent with these findings, experiments in RAW264.7 cells demonstrated that LBP downregulated pro‐inflammatory cytokines IL‐1β, IL‐6, and iNOS, while upregulating anti‐inflammatory IL‐10 and Arg‐1. Further mechanistic analysis revealed that LBP modulates macrophage polarization by regulating the phosphorylation of STAT1 and STAT6, thereby promoting the M2 phenotype and inhibiting M1 activation. Collectively, these results indicate that LBP attenuates SA‐AKI by regulating macrophage polarization.