Codonopsis pilosula polysaccharide attenuates Brucella OMP19-induced macrophage inflammation via ATP2A1, cell adhesion, and calcium signaling.

Brucellosis, a significant zoonotic disease, poses a global health challenge, primarily due to the pathogen's ability to evade macrophage-mediated killing and trigger a detrimental pro-inflammatory cytokine storm. Current treatments often struggle with bacterial persistence and immune-mediated tissue damage. Polysaccharides from traditional medicinal plants, like Codonopsis pilosula, have shown promise in modulating immune responses and inhibiting inflammation, making them attractive candidates for exploring novel therapeutic strategies against persistent infections and associated inflammatory pathologies.

Researchers investigated the anti-inflammatory effects of Codonopsis pilosula polysaccharides (CPPS) against Brucella abortus outer membrane protein 19 (OMP19)-induced inflammation. The study employed both in vivo and in vitro models. In vivo, CPPS was administered to an unspecified animal model of brucellosis, with tissue damage and protein expression (HMGB1, E-cadherin, paxillin) as key endpoints. In vitro, macrophages were stimulated with OMP19, and the impact of CPPS on various signaling pathways (SYK/FAK/AKT, PKC, WNT-1), cytokine profiles (TNF-α, IL-6, IL-10), cell adhesion markers, and intracellular calcium (Ca2+) concentration was assessed. Transcriptome sequencing identified ATP2A1 as a key gene, further validated by knockdown experiments to confirm its role in CPPS's anti-inflammatory actions.

CPPS demonstrated significant anti-inflammatory effects across both in vivo and in vitro models. In vivo, CPPS markedly alleviated tissue damage and downregulated the expression of HMGB1, E-cadherin, and paxillin. In vitro, CPPS inhibited SYK/FAK/AKT phosphorylation, PKC activation, and WNT-1 signaling pathway transduction. The cytokine profile was also modulated, with CPPS downregulating pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10. Furthermore, CPPS decreased the expression levels of E-cadherin and paxillin and reduced the intracellular calcium ion (Ca2+) concentration. Transcriptome sequencing identified ATP2A1 as a key differentially expressed gene. > Knockdown experiments confirmed that CPPS exerts its anti-inflammatory effects by regulating ATP2A1, highlighting a novel mechanism involving cell adhesion and calcium signaling modulation.