FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect on DSS-induced colitis via the 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 junctions 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 peptides in the 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 colitis in mice, such as weight loss, disease activity index (DAI), colon shortening, spleen hypertrophy, histological scores, and MPO activity. FSGHF3 and peptide treatment inhibits pro-inflammatory cytokine 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 the removal of ROS and inhibition of NF-kappa B activation. Overall, our results suggest that FSGHF3 and peptides may be promising potential candidates for the alleviation of colitis.