Anti‐Inflammatory Peptides as Promising Therapeutics Agent Against Inflammatory Bowel Diseases: A Systematic Review

ABSTRACT Background Inflammatory bowel disease (IBD) is linked to dysregulated mucosal immunity, microbiota imbalances, and environmental factors, though its exact cause remains unknown. Current treatments often have limitations, necessitating innovative therapies. This review evaluates anti‐inflammatory peptides (AIPs) as emerging therapeutic agents, focusing on their efficacy in Ulcerative Colitis and Crohn's disease. Methodology A systematic review was conducted in February 2023, adhering to PRISMA 2020 guidelines. Studies published from 2010 to 2023 on AIPs for IBD treatment were retrieved from Medline, Web of Science, and Cochrane databases using keywords such as IBDs, AIPs, Crohn's disease, Ulcerative Colitis, and therapy. Results Seventeen studies met the inclusion criteria, comprising 12 animal studies, four clinical trials, and one case–control study. H‐SN1 (snake venom peptide) and GLP‐2② (glucagon‐like peptide‐2 dimer) effectively inhibited TNF cytotoxicity. Oral AVX‐470 (bovine‐derived anti‐TNF antibody) reduced enterocyte TNF, MPO, and apoptosis levels. Ac2‐26 (annexin A1 mimic) and αs2‐casein peptide combined with synbiotics were shown to restore gut homeostasis and dysbiosis. AMP‐18 (gastrokine‐1) and MBCP (buffalo milk peptide) stabilized tight junctions, preserving intestinal barrier integrity and potentially preventing IBD progression. Conclusion AIPs effectively reduce inflammation, regulate gut microbiota, and stabilize the intestinal barrier, showing promise for managing IBD. However, their therapeutic potential is limited by protease degradation, poor bioavailability, and possible cytotoxicity. Future research should enhance their stability, delivery systems, and pharmacokinetic properties to optimize their clinical applicability and safety.