Curcumin prevents and ameliorates trinitrobenzene sulfonic acid–induced colitis in mice

doi:10.1053/gast.2002.37050

Gastroenterology

Volume 123, Issue 6, December 2002, Pages 1912-1922

https://doi.org/10.1053/gast.2002.37050 Get rights and content

Abstract

Background & Aims: Curcumin is known to have a variety of pharmacologic effects, including antitumor, anti-inflammatory, and anti-infectious activities. The pleiotropic effects of curcumin are attributable at least in part to inhibition of transcriptional factor nuclear factor κB (NF-κB). However, the effect of curcumin on intestinal inflammation has hitherto not been evaluated. The aim of this study was to determine whether treatment with curcumin prevents and ameliorates colonic inflammation in a mouse model of inflammatory bowel disease. Methods: Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis were treated with 0.5%, 2.0%, or 5.0% curcumin in the diet, and changes in body weight together with histologic scores were evaluated. Colonic T-cell subsets were characterized, and NF-κB in colonic mucosa was detected by immunohistochemistry. NF-κB activity in the colonic mucosa was evaluated using electrophoretic mobility shift assay. Cytokine messenger RNA expression in colonic tissue was assessed by semiquantitative reverse-transcription polymerase chain reaction. Results: Treatment of mice with curcumin prevented and improved both wasting and histopathologic signs of TNBS-induced colonic inflammation. Consistent with these findings, CD4⁺ T-cell infiltration and NF-κB activation in colonic mucosa were suppressed in the curcumin-treated group. Suppression of proinflammatory cytokine messenger RNA expression in colonic mucosa was also observed. Conclusions: This study has shown for the first time that treatment with curcumin can prevent and improve murine experimental colitis. This finding suggests that curcumin could be a potential therapeutic agent for the treatment of patients with inflammatory bowel disease.

GASTROENTEROLOGY 2002;123:1912-1922

Section snippets

Animals

In this study, 7- to 8-week-old male C57BL/6 and BALB/c mice (Japan SLC Co., Hamamatsu, Japan) weighing 21–23 g were used. All mice were maintained under specific pathogen-free conditions in our own animal facilities and handled according to institutionally recommended animal care guidelines.

Diet and reagents

Curcumin (purity, 99.9%) was purchased from Nacalai Tesque, Inc. (Kyoto, Japan). For dietary administration, curcumin was mixed with the diet to concentrations of 0.5% (wt/wt), 2.0%, or 5.0%. Mice were fed

Preventive curcumin therapy improves the mortality rate of mice with TNBS-induced colitis

In the present study, the mortality rate of C57BL/6 mice with TNBS-induced colitis was 35.5%, although that of control mice (administration of 50% ethanol without TNBS) was 0% (Figure 1).

. Preventive curcumin therapy protects against death after administration of TNBS. Values in parentheses indicate the number of surviving animals compared with the total number of animals 7 days after administration of TNBS. Results are shown as the mean mortality rate for each experimental group.

In early

Discussion

From the findings described in this report, we drew the following conclusions concerning the effect of curcumin on TNBS-induced colitis. (1) Curcumin is able to completely prevent death due to TNBS-induced colitis. (2) Administration of curcumin significantly attenuates both wasting disease and colonic inflammation induced by TNBS. (3) Treatment with curcumin markedly reduces CD4⁺ T-cell infiltration in the lamina propria. (4) NF-κB activation in colonic mucosa is suppressed by treatment with

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^☆: Address requests for reprints to: Yukio Koide, M.D., Ph.D., Department of Microbiology and Immunology, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Hamamatsu 431-3192, Japan. e-mail: [email protected]; fax: (81) 53-435-2335.

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Basic–Alimentary TractCurcumin prevents and ameliorates trinitrobenzene sulfonic acid–induced colitis in mice☆

Abstract

Section snippets

Animals

Diet and reagents

Preventive curcumin therapy improves the mortality rate of mice with TNBS-induced colitis

Discussion

Gastroenterology

Gastroenterology

Immunol Today

Gastroenterology

Gastroenterology

Am J Gastroenterol

Cancer Lett

Cancer Lett

J Biol Chem

Biochem Pharmacol

J Nutr

Anal Biochem

Eur J Pharmacol

Gastroenterology

Food Chem Toxicol

Toxicology

Toxicology

Mucosal immunoregulation and inflammatory bowel disease: new insights from murine models of inflammation

Scand J Immunol

Insights from mouse models of colitis

J Leukoc Biol

Cytokines in inflammatory bowel disease

World J Surg

The NF-κB and IκB proteins: new discoveries and insights

Annu Rev Immunol

Role of NF-κB in immune and inflammatory responses in the gut

Gut

Activation of nuclear factor κB inflammatory bowel disease

Gut

Basic–Alimentary Tract
Curcumin prevents and ameliorates trinitrobenzene sulfonic acid–induced colitis in mice☆