Oyster peptides for relieving ulcerative colitis: A combination of cell experiments and network pharmacology screening

Ulcerative colitis (UC), an inflammatory bowel disease, is characterized by inflammation and oxidative stress. Oyster, a high-nutrition mariculture shellfish, is a vital source of bioactive peptides. This study aimed to excavate oyster-derived peptides to alleviate dextran sulfate sodium (DSS)-induced UC. Combined cell assays and network pharmacology, it was found that both FR8 (FAGDDAPR) and GR9 (GFAGDDAPR) significantly alleviated DSS-induced NCM460 cell injury, enhanced viability, and exerted anti-inflammatory and antioxidant effects. At 1 μg/mL, FR8 reduced IL-6, TNF-α and ROS by 11.58 ± 3.08%, 21.52 ± 0.75% and 49.04 ± 0.82% respectively, and increased SOD activity by 41.62 ± 5.04%. While GR9 exerted corresponding effects of 12.10 ± 5.72%, 22.16 ± 1.05%, 50.56 ± 0.83%, and 41.41 ± 4.59%. Molecular dynamics simulations clarified their intermolecular interaction with caspase-1. These findings support FR8 and GR9 as UC-mitigating functional food ingredients, and provide a theoretical basis for high-value utilization of oyster peptide resources.