135 FH and FGSH prepared from fish skin gelatin using ginger protease alleviates 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. Hence, it is important to apply new strategies to cope with the IBD. We previously found that hydrolysate fractions (HF) and fish skin gelatin hydrolysate (FSGH), isolated from fish skin gelatin hydrolysate using ginger protease, could exert antioxidant effects in IPEC-J2 cells. Here, we aimed to evaluate the effects of FH and FGSH in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mouse were treated with 3% DSS in their drinking water for 7 days to induce acute colitis. FH (200 mg/kg) and FGSH (200 mg/kg) was administered for 7 days before and during DSS treatment via oral gavage once per day. Mouse were sacrificed at day 7 after colitis induction. The results showed that FH and FGSH significantly ameliorated the clinical symptoms of DSS-induced mice colitis, such as weight loss, disease activity index (DAI), colon shortening, spleen hypertrophy and histological scores. For MPO activity, an important indicator of neutrophil infiltration and acute inflammation in DSS-induced mouse colitis, FH and FGSH significantly reduced the level of DSS-induced hyperactivated MPO. Treatment with FH and FGSH also significantly inhibited the secretion proinflammatory cytokines TNF-α, IL-8 and IL-12 in DSS-induced mouse colitis. And FH and FGSH administration significantly increased expression of antioxidant enzymes GCLM, GCLC and GPX4 and maintained tight junction in colon tissues. Furthermore, we found that FH and FGSH significantly increased the level of Nrf2 in colon tissues, it indicated that FH and FGSH may alleviated colitis by Nrf2 pathway. Overall, these results suggested that FH and FGSH could be a potential promising candidate for the treatment of IBD.