linagliptin has been researched along with Colitis* in 2 studies
2 other study(ies) available for linagliptin and Colitis
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Linagliptin ameliorates acetic acid-induced colitis via modulating AMPK/SIRT1/PGC-1α and JAK2/STAT3 signaling pathway in rats.
Ulcerative colitis is a chronic inflammatory disease, profoundly affecting the patient's quality of life and is associated with various complications. Linagliptin, a potent DPP- IV inhibitor, shows favorable anti-inflammatory effects in several animal model pathologies. To this end, the present study aimed to investigate the anti-inflammatory effect of linagliptin in a rat model of acetic acid-induced colitis. Moreover, the molecular mechanisms behind this effect were addressed. Accordingly, colitis was established by the administration of a 2 ml 6% acetic acid intrarectally and treatment with linagliptin (5 mg/kg) started 24 h after colitis induction and continued for 7 days. On one hand, the DPP-IV inhibitor alleviated the severity of colitis as evidenced by a decrease of disease activity index (DAI) scores, colon weight/length ratio, macroscopic damage, and histopathological deteriorations. Additionally, linagliptin diminished colon inflammation via attenuation of TNF-α, IL-6, and NF-κB p65 besides restoration of anti-inflammatory cytokine IL-10. On the other hand, linagliptin increased levels of p-AMPK, SIRT1, and PGC-1α while abolishing the increment in p-JAK2 and p-STAT3. In parallel linagliptin reduced mTOR levels and upregulated expression levels of SHP and MKP-1 which is postulated to mediate AMPK-driven JAK2/STAT3 inhibition. Based on these findings, linagliptin showed promising anti-inflammatory activity against acetic acid-induced colitis that is mainly attributed to the activation of the AMPK-SIRT1-PGC-1α pathway as well as suppression of the JAK2/STAT3 signaling pathway that might be partly mediated through AMPK activation. Topics: Acetic Acid; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Colitis; Cytokines; Disease Models, Animal; Inflammation; Janus Kinase 2; Linagliptin; Male; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Signal Transduction; Sirtuin 1; STAT3 Transcription Factor | 2022 |
Linagliptin mitigates experimental inflammatory bowel disease in rats by targeting inflammatory and redox signaling.
Dipeptidyl peptidase-4 (DPP-4) has been involved in the pathogenesis of inflammatory bowel diseases (IBD), yet the underlying mechanisms remain inconclusive. The present study aimed to investigate the potential of linagliptin, a potent/selective DPP-4 inhibitor with marked anti-inflammatory actions, to attenuate trinitrobenzene sulfonic acid (TNBS)-evoked colitis in rats; an experimental model of IBD, and the implicated molecular mechanisms. This may add to the clinical utility of linagliptin for the management of patients with coexisting IBD and diabetes mellitus. Notably, no former studies have linked JAK2/STAT3, HMGB1/NF-κB, and Nrf2/HO-1 signaling in TNBS-evoked colitis.. Western blotting and ELISA were used to determine the levels of target signals.. Administration of linagliptin (1.5 mg/kg; p.o.) mitigated the colitis severity via diminishing the disease activity index, colon weight/length ratio, and macroscopic scores. Linagliptin also lowered the colonic histologic scores and leukocyte invasion. Notably, linagliptin inhibited the colonic DPP-4 activity and upregulated the expression of intestinotrophic GLP-2 without incurring hypoglycemia in animals. Linagliptin curbed inflammation through the suppression of colonic IL-6, TNF-α, and myeloperoxidase and upregulation of IL-10. It also inhibited the IL-6/JAK2/STAT3 pathway via downregulating p-JAK2/JAK2 and p-STAT3/STAT3 protein expression and HMGB1/RAGE/NF-κB cascade through lowering HMGB1, RAGE, and p-NF-κB p65/NF-κB p65 protein expression. In the context of mucosal oxidative stress, linagliptin diminished lipid peroxides and augmented GSH, GPx, and total antioxidant capacity. It also activated Nrf2/HO-1 pathway via upregulating Nrf2 and HO-1 protein expression.. Linagliptin shows a promise for the management of IBD via targeting IL-6/JAK2/STAT3, HMGB1/RAGE/NF-κB, and Nrf2/HO-1 pathways. Topics: Animals; Colitis; Cytokines; Hypoglycemic Agents; Inflammation; Inflammatory Bowel Diseases; Janus Kinase 2; Linagliptin; Male; NF-kappa B; Oxidation-Reduction; Rats; Rats, Wistar; Signal Transduction; STAT3 Transcription Factor; Trinitrobenzenesulfonic Acid | 2021 |