# Gut–Brain Metabolic Remodeling Mediates the Neuroprotective Effects of Combined Shrimp and Corn Peptides in Scopolamine-Induced Cognitive Impairment

## TL;DR

A combination of shrimp and corn peptides in a 1:1 ratio helps improve memory and brain function in mice with cognitive impairments, possibly through gut-brain interactions.

## Contribution

The study reveals the ratio-dependent neuroprotective effects of combined marine and plant peptides via gut-brain metabolic remodeling.

## Key findings

- The 1:1 ratio of QMDDQ and AGLPM most effectively restored cognitive function and hippocampal cholinergic activity.
- Peptide hydrolysis in the gut produced glutamate- and proline-rich fragments that influenced brain amino acid balance.
- The combination elevated BDNF, NGF, and NTF-3 expression, mitigating neuronal damage in the hippocampus.

## Abstract

(1) Background: Bioactive peptides from marine and plant sources show neuroprotective potential, yet how their combination ratios affect memory regulation via the gut–brain axis remains unclear. This study investigated the effects of different ratios of marine peptide QMDDQ (Glutamine-Methionine-Aspartate-Aspartate-Glutamine) and plant peptide AGLPM (Alanine-Glycine-Leucine-Proline-Methionine) on scopolamine-induced memory impairment in mice. (2) Methods: Cognitive function was assessed using the Morris water maze and novel object recognition tests. Nissl staining, microplate-based assays for acetylcholine (ACh) content and acetylcholinesterase (AChE) activity, Western blotting for neurotrophic factors, LC-MS/MS-based intestinal peptide profiling, and HPLC-based brain amino acid analysis were performed. (3) Results: The 1:1 ratio most effectively restored learning and memory, regulated hippocampal cholinergic function, mitigated neuronal damage, and elevated BDNF, NGF, and NTF-3 expression. In the gut, peptides were hydrolyzed into glutamate- and proline-rich fragments, which influenced brain amino acid balance by elevating glutamate and proline levels while reducing NH3-related signaling. (4) Conclusions: These results highlight the ratio-dependent efficacy of QMDDQ-AGLPM combinations and provide evidence for a gut peptide remodeling-brain metabolic link relevant to cognitive impairment.