Canagliflozin ameliorates ulcerative colitis via regulation of TLR4/MAPK/NF- κB and Nrf2/PPAR-γ/SIRT1 signaling pathways

This study aims to provide insights into the potential benefits of canagliflozin as a treatment for UC by addressing possible cellular signals. Acetic acid (AA; 4% v/v) was administered intrarectally to induce colitis. Canagliflozin is given orally at a dose of 10 mg/kg/day. Canagliflozin attenuates inflammation in AA-induced colitis, evidenced by significant and dose-dependently downregulation of p38 MAPK, NF-κB-p65, IKK, IRF3, and NADPH-oxidase as well as colonic levels of IL-6 and IL-1β and MPO enzymatic activity. Canagliflozin mitigates colonic oxidative stress by decreasing MDA content and restoring SOD enzymatic activities and GSH levels mediated by co-activating of Nrf2, PPARγ, and SIRT1 pathways. Moreover, an in-silico study confirmed that canagliflozin was specific to all target proteins in this study. Canagliflozin's binding affinity with its target proteins indicates and confirms its effectiveness in regulating these pathways. Also, network pharmacology analysis supported that canagliflozin potently attenuates UC via a multi-target and multi-pathway approach.PMID:37898288 | DOI:10.1016/j.ejphar.2023.176166

Source: European Journal of Pharmacology - October 28, 2023 Category: Drugs & Pharmacology Authors: Hanan S Althagafy Fares E M Ali Emad H M Hassanein Zuhair M Mohammedsaleh Mohamed I Kotb El-Sayed Ahmed M Atwa Ahmed M Sayed Ayman A Soubh Source Type: research