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.

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.

Related Concept Videos

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
384
Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
379
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
392