Beef tripe-derived peptides ameliorate ulcerative colitis in mice via the MAPK signaling pathway and modulating disorder of gut metabolism

Beef tripe is rich in high-quality protein, and its enzymatically hydrolyzed peptides exhibit diverse physiological activities. This study investigated their therapeutic potential against dextran sulfate sodium-induced colitis in mice, focusing on three peptides derived from beef tripe (NLPLPPPPPPR, GLGPPSPPAPPR, and HSLPPGPY). Results demonstrated that these peptides alleviated ulcerative colitis symptoms, including reduced weight loss, lower inflammation markers (disease activity index scores, rectal bleeding), improved mental status, and repaired colonic mucosal damage. They also decreased intestinal inflammation, reduced immune cell infiltration (macrophages, neutrophils), and strengthened intestinal barrier function. Mechanistically, peptides inhibited the mitogen-activated protein kinase (MAPK) pathway (JNK, TLR4, p38, ERK phosphorylation), suppressing inflammation. Metabolomic analysis revealed 55 restored gut metabolites critical to anti-inflammatory effects. Overall, beef tripe peptides effectively alleviated colitis by blocking MAPK signaling, restoring gut metabolism, and reducing inflammation, offering a potential therapeutic strategy for ulcerative colitis.