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Published on: September 12, 2019
Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and
Jianhua Gao1, Jian Cui2, Haiqing Zhong2
1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China; State Key Laboratory of Innovative Nature Medicine and TCM Injections, Ganzhou, China.
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.
Insights
Andrographolide sulfonate significantly reduced mortality and inflammation in mice with chronic colitis. This natural compound mitigated colonic damage and fibrosis, suggesting its potential for treating inflammatory bowel disease.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Inflammatory bowel disease (IBD) presents with diarrhea, abdominal pain, and potential fibrosis.
- Andrographolide sulfonate's efficacy in acute experimental colitis is established.
- Chronic colitis models are crucial for evaluating long-term therapeutic effects.
Purpose of the Study:
- To investigate the therapeutic potential of andrographolide sulfonate in a chronic murine colitis model.
- To assess andrographolide sulfonate's impact on inflammation, immune cell infiltration, and tissue damage.
- To explore the molecular mechanisms underlying andrographolide sulfonate's anti-inflammatory effects.
Main Methods:
- Chronic colitis was induced in mice via repeated intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS).
- Mice were treated with andrographolide sulfonate, and outcomes including mortality, cytokine levels, immune cell infiltration, and tissue histology were analyzed.
- Key signaling pathways (p38, p65) and immune cell subsets (Th1, Th17) were evaluated.
Main Results:
- Andrographolide sulfonate treatment significantly decreased mortality in TNBS-induced chronic colitis.
- Colonic levels of inflammatory cytokines (IL-6, IL-17A, TNF-α, IFN-γ) were reduced.
- Treatment suppressed CD4+ T cell and macrophage infiltration, including pathogenic Th1 and Th17 subsets.
- Epithelial damage and fibrosis were significantly mitigated, alongside the inhibition of p38 and p65 activation.
Conclusions:
- Andrographolide sulfonate effectively ameliorates chronic colitis in mice by reducing inflammation, epithelial damage, and fibrosis.
- The compound demonstrates potential as a therapeutic agent for chronic inflammatory bowel disease.
- Further clinical investigations into andrographolide sulfonate for colitis treatment are warranted.
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