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In Vivo Atlas of Neuroprotective Cyclic Dipeptides Derived from Food Gelatin Using Peptidomics and Feature-Based Molecular Networking

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Food gelatin is widely used in the food industry, yet its in vivo active substances remain unclear. This study proposes a strategy for in vivo research on donkey-hide gelatin that integrates peptidomics, feature-based molecular networks (FBMN), and targeted spatiotemporal metabolomics to address the above issues. Peptidomics based on database searching revealed a time-dependent decrease in peptide numbers and an increase in oligopeptide ratios in the small intestine over 24 h, with oligopeptides increasing from 50 to 100%. FBMN visualization in serum allowed the first identification of cyclodipeptides (CDPs) originating from gelatin. Targeted metabolomics detected 35 CDPs in serum, with 12 proline/hydroxyproline-CDPs being particularly abundant. Spatiotemporal analysis revealed different distributions of CDPs in the gastrointestinal and serum, and they showed prolonged retention in vivo . Twelve proline/hydroxyproline-CDPs displayed neuroprotective effects in HT-22 cells, with cyclo(Hyp-Ala) showing the highest efficacy. This study presents a strategy for identifying exogenous bioactives in complex matrices, applicable to other food proteins.

Source: Journal of Agricultural and Food Chemistry

DOI: 10.1021/acs.jafc.5c08112