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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...
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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...
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Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
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Combination Therapy with Indigo and Indirubin for Ulcerative Colitis via Reinforcing Intestinal Barrier Function.

Jin Xie1, Shimin Tian1, Jun Liu1

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Combined indigo and indirubin treatment significantly improves ulcerative colitis (UC) symptoms by enhancing intestinal barrier function and regulating immune responses. This synergistic approach offers a promising therapeutic strategy for UC management.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Immunology

Background:

  • Indigo and indirubin, active compounds in Indigo naturalis, show therapeutic potential for ulcerative colitis (UC).
  • These isomers possess distinct mechanisms including anti-inflammation, immune, microbiota, and oxidative stress regulation, and mucosal repair.
  • Understanding their combined administration's synergistic effects is crucial for UC treatment.

Purpose of the Study:

  • To investigate the efficacy and underlying mechanisms of combined indigo and indirubin administration in colitis mouse models.
  • To elucidate how the combination therapy impacts intestinal barrier function, immune responses, and gut microbiota.

Main Methods:

  • Administration of indigo, indirubin, and their combination to mouse models of colitis.
  • Assessment of disease symptoms, intestinal barrier integrity (E-cadherin, occludin, ZO-1, MUC2), and intestinal permeability.
  • Analysis of cytokine expression (TNF-α, IFN-γ, IL-12, IL-23, IL-17A), immune cell infiltration, and reactive oxygen/nitrogen species (ROS/RNS) production.
  • Evaluation of immune cell populations (NK cells, ILC3, neutrophils, dendritic cells) and gut microbiota composition.

Main Results:

  • Combined indigo and indirubin demonstrated superior improvement in colitis symptoms compared to individual treatments.
  • The combination therapy significantly reinforced intestinal barrier function and reduced intestinal permeability.
  • All treatments modulated cytokine expression and reduced immune cell infiltration and ROS/RNS production, with indirubin showing potent anti-inflammatory effects.
  • Indigo showed a stronger capacity for regulating specific immune cells, while the combination synergistically enhanced overall immune modulation and microbiota composition.

Conclusions:

  • Indigo and indirubin exhibit synergistic effects in treating colitis, primarily by reinforcing intestinal barrier function.
  • The combined therapy integrates indirubin's anti-inflammatory and microbiota-regulating strengths with indigo's immune and ROS/RNS regulatory advantages.
  • This synergistic approach presents a promising therapeutic strategy for ulcerative colitis by addressing multiple pathological pathways.