Tricholoma matsutake Protein as a Novel Cognitive Supportive Nutrient: Identification and Molecular Interaction Mechanism Study of Memory-Enhancing Peptides.

Mice receiving Tricholoma matsutake powder (TP), its protein fraction (TPT), or polysaccharide fraction (TPS) showed superior cognitive performance compared with controls after 30 days of supplementation.

• Supplementation duration was 30 days of daily dietary supplementation.
• Cognitive assessments included object recognition, spatial learning, and working memory tasks.
• TPT demonstrated the most pronounced improvement among the three supplementation groups.
• Controls showed inferior performance on all three cognitive measures relative to all supplemented groups.

TPT supplementation promoted hippocampal neuronal morphological integrity and increased Nissl body density compared with controls.

• Morphological integrity of hippocampal neurons was assessed histologically.
• Nissl body density was increased in TPT-supplemented mice.
• TPT showed the strongest efficacy among the bioactive components tested.
• These histological findings were associated with the superior cognitive performance observed in TPT-supplemented animals.

TPT supplementation enhanced cholinergic function and markedly reduced oxidative stress in mice.

• Cholinergic function was enhanced in TPT-supplemented mice relative to controls.
• Oxidative stress was markedly reduced with TPT supplementation.
• These effects were more pronounced with TPT than with TP or TPS.
• Enhanced cholinergic function is consistent with a potential mechanism involving acetylcholinesterase (AChE) inhibition.

LC-MS/MS analysis identified 2287 peptides in TPT digestion products, of which 168 were stable peptides with potential memory-enhancing activity after in vitro digestion and absorption assays.

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for peptide identification.
• Total peptides identified in TPT digestion products: 2287.
• In vitro digestion and absorption assays were used to screen for stability and bioavailability.
• 168 stable peptides were identified as having potential memory-enhancing activity after screening.

Molecular docking revealed that peptides PFL (Pro-Phe-Leu), LFL (Leu-Phe-Leu), and AFL (Ala-Phe-Leu) interact with acetylcholinesterase (AChE) binding sites with high docking scores and stable binding.

• Three tripeptides—PFL, LFL, and AFL—were identified as candidate AChE inhibitors through molecular docking.
• Multiple interactions were identified between each peptide and AChE binding sites.
• Docking scores were described as high and binding as stable for all three peptides.
• These peptides were highlighted as 'more promising candidate molecules for preventing MCI.'

Increasing evidence links dietary supplementation to cognitive health, and prior studies have focused primarily on alleviating mild cognitive impairment (MCI) through edible mushroom supplementation, leaving knowledge gaps regarding cognitive support in healthy individuals.

• The study framed maintaining or enhancing cognitive function in healthy individuals as essential for preventing neurodegenerative diseases.
• Prior research emphasis on MCI alleviation was identified as leaving 'substantial knowledge gaps.'
• This study specifically examined effects on mouse cognitive function in the context of daily dietary supplementation.
• Tricholoma matsutake was examined as a novel cognitive supportive nutrient.