Alanyl‐glutamine Heals Indomethacin‐induced Gastric Ulceration in Rats Via Antisecretory and Anti‐apoptotic Mechanisms

ABSTRACT Objectives: Alanylglutamine (AG) is a dipeptide that fuels enterocytes and has a coadjuvant role during gut healing. The current study aimed to investigate the potential ulcer‐healing effect of AG in indomethacin‐induced gastropathy. Methods: Animals (n = 10 rats/group) were randomly allocated into 5 groups. Gastric ulcerated rats were administered AG, AG + dexamethasone, or pantoprazole after indomethacin exposure. Results: Comparable to pantoprazole, AG inhibited H + ‐K + ATPase pump, and elevated the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of glucagon‐like peptide‐1 (GLP‐1), p S473‐Akt, and cyclin‐D1. On the contrary, AG abated serum tumor necrosis factor‐α and gastric mucosal content of p S45‐β catenin, p S9‐GSK3β, p S133‐CREB, p S536‐NF‐κB, H 2 O 2 , claudin‐1, and caspase‐3. The administration of dexamethasone before AG hampered its effect on almost all the measured parameters. Conclusions: AG confers its antiulcerogenic/antisecretory potentials by repressing the proton pump to increase the gastric juice pH via boosting p‐ CREB, p ‐Akt, p ‐GSK‐3β, and GLP‐1. Also, it inhibits apoptosis through suppressing nuclear factor‐kappa B/tumor necrosis factor‐α/H 2 O 2 /claudin‐1 cue. This trajectory contributes to loosen the tight junction priming AG‐mediated GLP‐1/β‐catenin/cyclin‐D1 that results in pronounced increase in gastric mucosa proliferation. Therefore, the crosstalk between multiple pathways orchestrates the action of AG against gastric ulceration.