Ganoderma lucidum polysaccharide alleviates cognitive dysfunction by inhibiting neuroinflammation via NLRP3/NF-κB signaling pathway

Ethnopharmacological relevance: Ganoderma lucidum (G. lucidum), a traditional Chinese medicinal herb, is commonly recommended for its potential to promote mental relaxation and alleviate memory impairment. Recently, there have been reports suggesting that it exhibits anti-neuroinflammatory activity through the gutbrain axis. Cognitive dysfunction is among the most prevalent neurodegenerative diseases. Aim of the study: This study aimed to investigate the efficacy of polysaccharides extracted from G. lucidum in alleviating cognitive dysfunction. Methods and materials: A polysaccharide was extracted through the process of alkali extraction followed by alcohol precipitation. Comprehensive analysis was conducted to characterize the total sugar content, amino acid composition, and sugar chain structure. The levels of inflammatory related factors were assessed using griess reagent, qPCR and western blotting assay in vitro. The efficacy of alleviating cognitive dysfunction was evaluated through a series of behavioral studies in mice model induced by the high-fat high-sugar diet combined with chronic unpredictable mild stress (HFFD/CUMS) in vivo. The mechanism was investigated by 16S rRNA sequence, immunohistochemistry, flow cytometry and short-chain fatty acid detection. Results: Ganoderma lucidum polysaccharide (GLP) is a polysaccharide identified as beta-glucan. Bioactivity experiments have demonstrated that GLP possesses the potential to ameliorate cognitive dysfunction. The mechanism study revealed that GLP can modulate the composition of gut microbiota and suppress the activation of inflammasomes via NLRP3/NF-kappa B signaling pathway, thereby attenuating neuroinflammatory. Furthermore, GLP may enhance the peripheral immunity response of the body, leading to a comprehensive regulatory effect. Conclusion: A polysaccharide alleviates cognitive dysfunction via inhibiting neuroinflammation.