Characterization and screening of a novel octapeptide from protein hydrolysates of Crassostrea gigas and its immunomodulatory effects on RAW264.7 cells

Food-derived bioactive peptides show great potential for functional foods, given their structural adaptability and safety. <i>Crassostrea gigas</i> contains abundant bioactive proteins, but the immunomodulatory mechanism of their peptides remains unclear. In this research, 29 new peptides were identified from papain-hydrolyzed oyster extracts using LC-MS/MS, and target peptide SWDNFLQR with high activity potential was obtained through bioinformatics screening and chemically synthesized. The immunomodulatory properties of SWDNFLQR were assessed through the RAW264.7 cells model and iTRAQ quantitative proteomics. SWDNFLQR enhanced proliferation, phagocytosis, and secretion of NO, TNF-α, and IL-6. It activates Toll-like receptors and the PI3K-Akt signaling pathway, modulating key proteins Fn1 and Prkacb. Notably, higher concentrations of SWDNFLQR specifically inhibited NF-κB pathway activation, indicating its dual immunomodulatory role in stimulating immune responses and mitigating excessive inflammation. This positions SWDNFLQR as a valuable component for the formulation of anti-inflammatory and immune-regulating functional foods.