Codonopsis pilosula polysaccharides mitigates Brucella abortus outer membrane protein 19-induced uterine damage via macrophage adhesion and calcium signaling

Brucellosis is a zoonotic disease caused by the Brucella species. Its pathogenesis is closely linked to bacterial evasion of macrophage-mediated killing, induction of a pro-inflammatory cytokine storm, and immune-mediated pathological damage. Accumulating evidence indicates that Codonopsis pilosula polysaccharides (CPPS) inhibits inflammatory signaling, enhances macrophage phagocytosis, and exerts immunomodulatory effects across multiple organs. However, the therapeutic potential of CPPS against brucellosis remains largely unexplored. Overall design: This study aimed to explore the effects of CPPS on inflammatory response induced by Brucella outer membrane protein 19 (OMP19). In vivo, CPPS significantly alleviated tissue damage and HMGB1 expression in the mouse uterus induced by OMP19. In vitro, CPPS inhibited the SYK/FAK/AKT phosphorylation, PKC activation, and Wnt-1 signaling pathway transduction. Additionally, CPPS also modulated the cytokine profile, downregulating pro-inflammatory cytokines (TNF-a, IL-6) while increasing anti-inflammatory IL-10 levels. Furthermore, CPPS decreased the levels of paxillin and E-cadherin, and reduced the intracellular calcium ion (Ca²?) concentration. Collectively, these findings indicate that CPPS mitigates OMP19-triggered uterine damage by regulating macrophage adhesion and calcium-dependent signaling, highlighting its potential as a therapeutic agent against brucellosis. Control: Untreated (mouse primary peritoneal macrophages) CPPS+OMP: Stimulated with CPPS and OMP19 (mouse primary peritoneal macrophages) OMP: Stimulated with OMP19 (mouse primary peritoneal macrophages)