Exploring the Anti-Inflammatory Effects and Molecular Mechanisms of Novel Peptides from Coregonus Peled : An Integrated Approach Combining In Silico and In Vitro

Inflammation is a key pathological process in chronic diseases. This study investigated the anti-inflammatory potential of bioactive peptides from Coregonus peled, a cold-water fish rich in protein. Among the six hydrolysates, Neutrase hydrolysates (NH) showed superior efficacy in reducing inflammation in LPS-induced RAW 264.7 macrophages. Amino acid composition analysis suggested that NH could be used as a potential source of anti-inflammatory peptides. Utilizing a combined approach of peptidomics and bioinformatics, four novel peptides, FGPPGPPTRPS (P1), AMPPPVRP (P2), PPPPTIPR (P3), and DRPGPPGGP (P4), were identified within NH, with P2 exhibiting the most potent anti-inflammatory activity. Integrated analyses of network pharmacology, proteomics, and molecular docking indicated that the cAMP signaling pathway was involved in the anti-inflammatory effect of peptide P2. Further validation using the PKA inhibitor H-89 demonstrated that the peptide P2 exerted its anti-inflammatory effect by inhibiting the cAMP/PKA/CREB signaling pathway. These findings highlight the potential of C. peled -derived peptides for functional foods or pharmaceutical applications.