Identification of novel oligopeptides from the simulated digestion of sea cucumber (Stichopus japonicus) to alleviate Aβ aggregation progression

The aim of this study was to isolate and identify peptides from sea cucumber hydrolysates prepared by simulated gastrointestinal digestion, and to evaluate the selected peptides against amyloid beta (Aβ) aggregation using a mCherry-Aβ (E22G) cells model. The sub-fraction (F2-b-2) with the highest ORAC value (17.48 μmol TE/mg peptides) and the strongest anti-Aβ aggregation rate (36.12%), was purified by gel permeation chromatography and ion exchange chromatography. Nine novel oligopeptides (GMR, DVE, VFP, IGFH, LGFH, FQF, ICK, LCK and DWF) were identified from F2-b-2. By molecular docking, four of them (IGFH, LGFH, DWF and FQF) showed promising CD38 inhibitory activity. Besides, these four peptides (0.1 and 0.5 mM) also demonstrated significant anti-Aβ aggregation activity as compared to the model group (p < 0.01). This research suggested that oligopeptides derived from sea cucumber could be used as candidates for anti-Aβ aggregation, as well as the prevention or treatment of Alzheimer's disease.