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ORAL ADMINISTRATION OF CURCUMIN HAS A POTENT ANTI-INFLAMMATORY EFFECT IN THE IL-10 GENE-DEFICIENT MOUSE
VY Ung, BC Sydora, RN Fedorak
Division of Gastroenterology, University of Alberta, Edmonton, Alberta
BACKGROUND: Curcumin is a water-insoluble polyphenol of the spice turmeric and has been thought to have beneficial health effects in humans. When mixed in with the food it has been shown to have preventative, as well as therapeutic, effects in chemically-induced murine colitis, potentially through the inhibition of pro-inflammatory gene expression. However, it is uncertain whether Curcumin has a similar effect in IL-10 gene-deficient mice which spontaneously develop inflammatory bowel disease (IBD). Carboxymethyl cellulose (CMC) is a food additive used as a viscosity modifier or thickener and is used to emulsify high concentrations of curcumin for oral administration.
Objective: The aim of this study is to investigate the effect of orally administered curcumin on the development of spontaneous colitis in the IL-10 gene deficient mouse.
METHODS: 12-13wk old IL-10 gene-deficient mice were gavaged daily for 2wk with: (i) 6mg (200mg/kg/d) curcumin, emulsified in 2% (w/v) CMC (curcumin/CMC), (ii) 2% CMC alone or (iii) water. Development of colitis was monitored by fecal occult blood testing and stool consistency. After 2wks of treatment, colonic histopathologic injury score, colonic weight/length (an indicator of intestinal inflammation), IFN-gamma and IL-17 release, and myeloperoxidase (MPO) activity were determined.
RESULTS: Curcumin/CMC- and CMC alone-fed mice both demonstrated similar reductions in fecal occult blood, stool consistency, and ratio of colon weight/length. This suggested that CMC alone may have a modifying effect on colitis in this model. Nevertheless, a significant reduction in pro-inflammatory cytokine (IL-17, IFNgamma) release in intestinal explant cultures was only seen in mice treated with Curcumin/CMC whereas CMC-treatment alone did alter production of these cytokines, p=0.007 for IFNgamma and p=0.02 for IL-17 for curcumin/CMC-treatment compared with control mice.
CONCLUSION: In the IL-10 gene-deficient mouse model of IBD, both oral curcumin and its emulsifying carrier, carboxymethyl cellulose, appear to have anti-inflammatory effects. However, curcumin has additional anti-inflammatory effects mediated through a reduced production of potent pro-inflammatory mucosal cytokines. An international clinical trial of curcumin in humans with IBD is currently ongoing.