Indirubin and isatin have been used in the treatment of inflammatory diseases due to their anti-inflammatory properties. This study aimed to evaluate the combined effect of indirubin and isatin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). UC was induced by the administration of 3% (w/v) DSS solution, and then the model mice were administered indirubin (10 mg/kg body mass) and (or) isatin (10 mg/kg body mass) by gavage once daily for 7 days. The results showed that indirubin and isatin, individually or combined, significantly inhibited weight loss, lowered disease activity index (DAI), ameliorated pathological changes, decreased the levels of pro-inflammatory mediators and myeloperoxidase (MPO) activity, increased the expression of anti-inflammatory cytokines and Foxp3, suppressed CD4 T cell infiltration, and inhibited oxidative stress and epithelial cell apoptosis. Additionally, indirubin and isatin, both individually and combined, can also inhibit activation of the NF-κB and MAPK pathways induced by DSS. The protective effect of combination therapy against UC was superior to that of single-agent treatment. These results suggest that indirubin combined with isatin attenuates DSS-induced UC, and changes to the NF-κB and MAPK signaling pathways may mediate the protective effects of indirubin and isatin in UC.

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http://dx.doi.org/10.1139/bcb-2018-0041DOI Listing

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Article Synopsis
  • Ulcerative colitis (UC) is a challenging inflammatory bowel disease with limited treatment options, prompting the need for safer and more effective drugs.
  • Recent studies show that 'Indigo naturalis' (IN), a traditional Chinese medicine, has strong anti-inflammatory, antioxidant, and immunomodulatory effects, making it a promising candidate for UC treatment.
  • Key components like indirubin and indigo from IN have been shown to effectively treat severe UC, but potential risks such as pulmonary hypertension highlight the need for careful use and further research on its therapeutic value.
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Indigo and indirubin are derived from indoxyl molecules, which generally occur as indoxyl glycosides in woad (Isatis tinctoria L.) and other indigo-producing plants. Indoxyl glycosides are biosynthesized from indole via 3-hydroxylation to form indoxyl, followed by one or more glycosylations.

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J Pharmacopuncture

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Department of Korean Medicine, College of Korea Medicine, Woosuk University, Jeonju, Republic of Korea.

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  • - This study explores the potential of IN compounds, particularly indirubin and indigo, as a novel treatment for Inflammatory Bowel Disease (IBD) by analyzing their pharmacological effects and mechanisms in preclinical models.
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The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc.

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