FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect in DSS-induced colitis via Nrf2 pathway

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. We previously found that fish skin gelatin hydrolysate fraction 3 (FSGHF3) isolated from fish skin gelatin hydrolysate, could exert antioxidant effects and maintain tight junction in IPEC-J2 cells. Further HPLC-ESI-QqQ-MS results revealed that this fraction mainly included some peptides. Here, we aim to evaluate the effects of FSGHF3 and peptide in mice model of dextran sodium sulfate (DSS)-induced colitis and LPS induced inflammation in IECs. The results show that FSGHF3 significantly ameliorates the clinical symptoms of DSS-induced mice colitis, such as weight loss, disease activity index (DAI), colon shortening, spleen hypertrophy, histological scores, and MPO activity. FSGHF3 and peptide treatment inhibits pro-inflammatory cytokines production, leading to the maintenance of intestinal architecture in vivo and in vitro. Meanwhile, FSGHF3 and peptide treatment promotes antioxidant enzyme expression via activating Nrf2, which results in removing ROS and inhibiting NF-κB activation. Overall, our results suggest that FSGHF3 and peptide may be a promising potential candidate for the alleviation of colitis.