Activity and mechanism of sea cucumber intestinal peptides in protecting and repairing gastric mucosa

This study investigated the protective and reparative effects of sea cucumber intestinal peptides (SCIPs) against ethanol-induced damage in human gastric mucosal epithelial cells (GES-1 cells) and explored the underlying mechanisms. SCIPs alleviated oxidative stress by reducing reactive oxygen species levels, increasing superoxide dismutase activity, and inhibiting malondialdehyde overproduction. Using a protein purification instrument and LC-MS/MS technology, peptides with a molecular weight of less than 1 kDa in the sea cucumber intestine were separated, purified, and identified, yielding a total of 91 peptide sequences. Using bioinformatics methods, the peptide PPPP with the best activity and drug-like properties is selected. Network pharmacology revealed that PPPP mainly exerts its biological functions by acting on core targets AKT1, EGFR, MAPK10, MAPK8, and IGF1R, regulating cancer pathways, PI3K-Akt signaling pathway, and lipid and atherosclerosis. Molecular docking and molecular dynamics simulations have confirmed that PPPP binds tightly to AKT1 through hydrogen bonds and hydrophobic interactions. The PPPP-AKT1 complex exhibits good stability, thereby effectively demonstrating its protective and reparative effects on the gastric mucosa. This study confirmed the protective and reparative effects of SCIPs on gastric mucosa and elucidated their underlying mechanisms, offering new insights for developing novel functional foods or pharmaceuticals.