Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and fibrosis

Int Immunopharmacol. 2020 Jun:83:106426. doi: 10.1016/j.intimp.2020.106426. Epub 2020 Mar 25.

Abstract

Inflammatory bowel disease could result in diarrhea and abdominal pain, as well as potential complications such as tissue fibrosis. The therapeutic effect of andrographolide sulfonate on acute murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) has been confirmed. In the study here, chronic colitis triggered by repeated intrarectal administration of TNBS was established and the effect of andrographolide sulfonate was examined. Repeated TNBS administration induced substantial mice death, which was significantly decreased by andrographolide sulfonate treatment. The elevation of inflammatory cytokines including IL-6, IL-17A, TNF-α as well as IFN-γ in colonic tissues levels were decreased after administration of andrographolide sulfonate. Next, CD4+ T cell and macrophage infiltration was found to descend. The subset of pathogenic CD4+ T cell subset including CD4+IFN-γ+ (Th1) and CD4+IL-17A+ (Th17) were also suppressed by andrographolide sulfonate. Further, the restrain of p38 and p65 activation were also observed after andrographolide sulfonate administration. Finally, TNBS-induced colonic epithelial damage as well as fibrosis were significantly mitigated by andrographolide sulfonate. Based on the results got here, we can make a conclusion that andrographolide sulfonate could decrease inflammation and epithelial damage as well as fibrosis thus ameliorating chronic colitis in mice. Our study suggest the possible use of andrographolide sulfonate for chronic colitis treatment in clinical.

Keywords: Andrographolide sulfonate; Chronic colitis; Fibrosis; TNBS.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / immunology
  • Colitis / pathology
  • Colon / drug effects
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • Colonic Diseases / metabolism
  • Colonic Diseases / pathology*
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Epithelium / drug effects
  • Epithelium / immunology
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • Fibrosis / metabolism
  • Inflammation / metabolism
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / metabolism
  • Trinitrobenzenesulfonic Acid / toxicity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Diterpenes
  • NF-kappa B
  • andrographolide
  • Trinitrobenzenesulfonic Acid
  • Mitogen-Activated Protein Kinases