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J Gastroenterol. 2017 Aug;52(8):904-919. doi: 10.1007/s00535-016-1292-z. Epub 2016 Nov 29.

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

Author information

1
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
2
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hiijima@gh.med.osaka-u.ac.jp.
3
Department of Inflammatory Bowel Disease, Osaka University Graduate School of Medicine, Suita, Japan.
4
Department of Gastroenterology and Hepatology, Sumitomo Hospital, Osaka, Japan.
5
Department of Gastroenterology and Hepatology, Higashiosaka City General Hospital, Higashiosaka, Japan.
6
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Abstract

BACKGROUND:

Indigo Naturalis (IN) is used as a traditional herbal medicine for ulcerative colitis (UC). However, the mechanisms of action of IN have not been clarified. We aimed to evaluate the efficacy of IN for ameliorating colonic inflammation. We further investigated the mechanisms of action of IN.

METHODS:

Colitis severity was assessed in dextran sodium sulfate-induced colitis and trinitrobenzene sulfonic acid-induced colitis models with or without the oral administration of IN or indigo, which is a known major component of IN. Colonic lamina propria (LP) mononuclear cells isolated from IN-treated mice were analyzed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. LP and splenic mononuclear cells cultured in vitro with IN or indigo were also analyzed. The role of the candidate receptor for indigo, the aryl hydrocarbon receptor (AhR), was analyzed using Ahr-deficient mice.

RESULTS:

Colitis severity was significantly ameliorated in the IN and indigo treatment groups compared with the control group. The mRNA expression levels of interleukin (Il)-10 and Il-22 in the LP lymphocytes were increased by IN treatment. The treatment of splenocytes with IN or indigo increased the expression of anti-inflammatory cytokines and resulted in the expansion of IL-10-producing CD4+ T cells and IL-22-producing CD3-RORĪ³t+ cells, but not CD4+Foxp3+ regulatory T cells. The amelioration of colitis by IN or indigo was abrogated in Ahr-deficient mice, in association with diminished regulatory cytokine production.

CONCLUSIONS:

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

KEYWORDS:

Aryl hydrocarbon receptor; Indigo; Indigo Naturalis; Inflammatory bowel disease; Ulcerative colitis

PMID:
27900483
DOI:
10.1007/s00535-016-1292-z
[Indexed for MEDLINE]

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