Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation

Kawai, Shoichiro; Iijima, Hideki; Shinzaki, Shinichiro; Hiyama, Satoshi; Yamaguchi, Toshio; Araki, Mikiya; Iwatani, Shuko; Shiraishi, Eri; Mukai, Akira; Inoue, Takahiro; Hayashi, Yoshito; Tsujii, Masahiko; Motooka, Daisuke; Nakamura, Shota; Iida, Tetsuya; Takehara, Tetsuo

doi:10.1007/s00535-016-1292-z

Cited by 94 publications

(80 citation statements)

References 43 publications

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“…As mentioned above, we did not observe any effect on DSS colitis despite previous papers describing alleviation of DSS colitis by IND [41,42]. The dose used was similar [41], but the preparation of IND used was different from ours, and this may have led to discrepancies in the results.…”

Section: Discussioncontrasting

confidence: 54%

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

Adachi

Hoshi²,

Inoue³

et al. 2017

Int Arch Allergy Immunol

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Background: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. Methods: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. Results: IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. Conclusions: Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).

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Section: Discussioncontrasting

confidence: 54%

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

Adachi

Hoshi²,

Inoue³

et al. 2017

Int Arch Allergy Immunol

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“…[24][25][26][27] More recently, IN has been shown to improve dextran sulfate sodium-induced colitis in a mouse model via an AhR/IL-22-mediated pathway. 28 However, recent studies have also shown other mechanisms of AhR signaling in terms of the induction of IL-10 receptor expression on intestinal epithelia, 29 IL-10 production in macrophages, 30 the induction of regulatory T cells, 31 and the negative regulation of the NLRP3 inflammasome. 32 Regardless, IN with different mechanisms from the current standard treatments may be beneficial for cases in which the efficacy of immunosuppressant or biologics is inadequate.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

et al. 2018

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“…For example, AhR ligands are crucial for activating AhR‐expressing type 3 innate lymphoid cells in the mucosa to produce IL‐22 . IL‐22 promotes mucosal healing by stimulating mucus production and goblet cell reconstitution under inflammatory conditions . Furthermore, AhR signaling has also been reported to induce immune tolerance with the production of IL‐10 .…”

Section: Discussionmentioning

confidence: 99%

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

Matsuno

Hirano

Torisu

et al. 2019

J of Gastro and Hepatol

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Background and Aim Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. Methods Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan–Meier method. Overall adverse events (AEs) during follow‐up were also analyzed. Results Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non‐responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow‐up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. Conclusions Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.

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Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation

Abstract: IN and indigo ameliorated murine colitis through AhR signaling activation, suggesting that AhR could be a promising therapeutic target for UC.

Cited by 94 publications

References 43 publications

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

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