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

Yudi Jiang; Zhe Wang; Wanshuai Wang; Yang Liu; Yang Meng; Yaozhong Wang; Minghao Fan; Chao Cai

doi:10.1016/j.jep.2024.119065

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

J Ethnopharmacol. 2024 Nov 8:119065. doi: 10.1016/j.jep.2024.119065. Online ahead of print.

Authors

Yudi Jiang¹, Zhe Wang¹, Wanshuai Wang¹, Yang Liu¹, Yang Meng², Yaozhong Wang², Minghao Fan³, Chao Cai⁴

Affiliations

¹ Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Carbohydrate-Based Drugs, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
² Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, 266001, Shandong, China.
³ Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Key Laboratory of Biological Fermentation Engineering of Beer, Tsingtao Brewery Co., Ltd, Qingdao, 266100, Shandong, China. Electronic address: fanmh@tsingtao.com.cn.
⁴ Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Carbohydrate-Based Drugs, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: caic@ouc.edu.cn.

PMID: 39522844
DOI: 10.1016/j.jep.2024.119065

Abstract

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 gut-brain 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 β-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-κB 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.

Keywords: Cognitive dysfunction; Ganoderma lucidum; Gut microbiota; Inflammasomes; Neuroinflammation; Polysaccharide.