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

TL;DR

Lycium barbarum polysaccharide reduces kidney damage in sepsis by shifting macrophages to an anti-inflammatory state.

Contribution

LBP's protective effect against sepsis-induced kidney injury is linked to macrophage polarization via STAT1/STAT6 regulation.

Findings

LBP reduced renal injury markers in sepsis-induced mice.

LBP shifted macrophage polarization from M1 to M2 in vivo and in vitro.

LBP modulated STAT1 and STAT6 phosphorylation to suppress inflammation.

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.

LBP extracted from
Lycium barbarum
modulates macrophage polarization toward the M2 type and suppresses the M1 type by promoting STAT6 phosphorylation and inhibiting STAT1 phosphorylation. This reduces IL‐1β and IL‐6 while increasing IL‐10, thereby alleviating sepsis‐associated acute kidney injury.

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