Yu-Ru Ren,Wen-Ting Cui,Kai-Li Jiang,Kai-Qi He,Yong-Ming Lu,Yan Chen,Wen-Juan Pan
Age-related cognitive decline is primarily attributed to the progressive weakening of synaptic function and loss of synapses, while age-related gut microbial dysbiosis is known to impair synaptic plasticity and cognitive behavior by metabolic alterations. To improve the health of the elderly, the protective mechanisms of Oudemansiella raphanipes polysaccharide (ORP-1) against age-related cognitive decline are investigated. The results demonstrate that ORP-1 and its gut microbiota-derived metabolites SCFAs restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by increasing the abundance of beneficial bacteria Dubosiella , Clostridiales , and Prevotellaceae and reducing the abundance of harmful bacteria Desulfovibrio , strengthen intestinal barrier integrity by abolishing age-related alterations of tight junction (TJ) and mucin 2 (MUC2) proteins expression, diminish age-dependent increase in circulating inflammatory factors, ameliorate cognitive decline by reversing memory- and synaptic plasticity-related proteins levels, and restrain hyperactivation of microglia-mediated synapse engulfment and neuroinflammation. These findings expand the understanding of prebiotic–microbiota–host interactions.
Age-associated increase in intestinal permeability is known to relate with gut microbiota dysbiosis and loss of epithelial tissue integrity. To improve healthy aging and prevent age-associated chronic disabilities, the protective potential of polysaccharides from Oudemansiella raphanipes (ORP-1) against age-associated intestinal epithelial barrier dysfunction in d -galactose-induced Caco-2 cells monolayer was investigated. In-vitro results demonstrated that ORP-1 can restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by facilitating the proliferation and adhesion of probiotics Lactobacillus acidophilus ( L. acidophilus ) and Bifidobacterium bifidum ( B. bifidum ) to compete with intestinal pathogenic Escherichia coli ( E. coli ) for ecological niches and nutrition. Meanwhile, ORP-1 strengthened the intestinal structural integrity primarily by abolishing the aggravation of apoptosis and the age-associated alterations of tight junction (TJ) proteins expression in intestine. These findings highlighted that ORP-1 could be a potential functional food component with preventive utility against age-associated intestinal barrier injury.
Oudemansiella raphanipesethanolic extract (ORE) was prepared via ultrasonication-assisted ethanolic extraction and enriched through silica gel and macroporous adsorption resin chromatography to afford a non-/weakly polar fraction (ORE-S) and a polar fraction (ORE-N), respectively. This study aimed to (1) quantify major bioactive components (e.g., polyphenols, alkaloids, and terpenes) in ORE-S and ORE-N, (2) assess their antioxidant activities, (3) correlate compositional differences with antioxidant function, and (4) identify key antioxidant compounds along with their potential mechanisms of action. By integrating widely targeted metabolomics with network pharmacology, we not only elucidated how enrichment methods influence the antioxidant properties of ORE but also demonstrated the potential of ORE-N as a valuable source of bioactive compounds and natural antioxidants.
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