Polysaccharides from Astragalus membranaceus Bunge alleviate LPS-induced neuroinflammation in mice by modulating microbe-metabolite-brain axis and MAPK/NF-κB signaling pathway.

Abstract

Neuroinflammation can lead to various neurodegenerative disorders, resulting in irreversible neurological dysfunction. Astragalus membranaceus Bunge polysaccharides (APS) present great potential in alleviating neuroinflammation; however, the specific mechanism underlying its neuroprotective effect remains unclear, leading to uncertain prospects for pharmaceutical applications. This study aims to elucidate the mechanism underlying APS-mediated inhibition of neuroinflammation in mice induced by lipopolysaccharide (LPS) through regulation of metabolic function, intestinal flora composition, and cell signaling transduction. Results indicated that APS pretreatment effectively mitigated LPS-induced brain damage. Metabolomics analysis revealed that APS pretreatment also regulated the metabolic disturbances induced by LPS through targeting five specific metabolic pathways. This regulation was supported by notable alterations in nine metabolite markers. Furthermore, APS pretreatment significantly modulated the abundance of four taxa of gut microbes (i.e., Romboutsia, Rikenella, Dubosiella, Odoribacter) closely associated with regulations in eleven metabolic and signaling pathways. Additionally, transcriptome analysis and Western blotting unveiled that APS pretreatment exerted a neuroprotective effect by modulating the MAPK/NF-κB signaling pathway. Our findings provide insights into the potential mechanisms underlying the neuroprotective effects of APS while establishing a solid foundation for future utilization of APS.