Novel Pentapeptide Derived from Chicken by-Product Ameliorates DSS-Induced Colitis by Enhancing Intestinal Barrier Function via AhR-Induced Src Inactivation

Managing patients with refractory inflammatory bowel diseases (IBD) is a common clinical challenge. Galli Gigeriae Endothelium Comeum (GGEC), a chicken by-product, has been used for centuries in Asian countries as a functional food and supplement for the treatment of gastrointestinal disorders. In this study, a novel peptide (LNLYP, LP-5) with gastrointestinal stability that can enhance the intestinal barrier function that was first identified in GGEC. Our work demonstrated that aryl hydrocarbon receptor (AhR) activation by LP-5 could inhibit the Src kinase to increase tight junction protein levels and down-regulate the expression of inflammatory cytokines to protect the intestinal barrier and finally alleviate dextran sulfate sodium (DSS)-induced colitis. This study revealed that LP-5 had the potential to develop into a therapeutic agent for the treatment of colitis and provided new high-valued utilization of GGEC.