Abstract
Inflammatory bowel diseases (IBDs) are caused by inflammation of the gastrointestinal tract, which may or may not have a specific cause or pathogen. They affect millions of people around the world and there are still few effective treatments. The aim of this work is to investigate anti-inflammatory effect of IKK-β inhibitor, LASSBio-1524, and its three analogues, LASSBio-1760, LASSBio-1763 and LASSBio-1764 in experimental animal models of intestinal inflammatory diseases, in mediators production and expression of inflammatory enzymes. Colitis was performed using two different models, which mimic Crohn's disease (induced by dinitrobenzene acid, DNBS) and ulcerative colitis (induced by sodium dextran sulphate, DSS) in mice. In both models was performed a therapeutic protocol with 1, 3 or 30 μmol/kg daily dose. LASSBio-1524 and its three analogues reduced the secretion of TNF-α, IL-1β, IL-6, IL-12, IFN-γ and increased secretion of IL-10, protecting gastrointestinal homeostasis. All compounds reduced macro and microscopic colonic damage caused by experimental colitis and p38 MAPK expression in the colon, as well as leukocytosis and anemia resulting from the disease. Our data may suggest LASSBio-1524 and its analogues (LASSBio-1760, LASSBio-1763 and LASSBio-1764) as promising candidates for new prototypes designed to inflammatory bowel diseases treatment.
- colon
- Gastrointestinal disorders
- gastrointestinal pharmacology
- inflammation
- inflammatory bowel disease (IBD)
- Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics