Skip to main content Accessibility help

Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice

  • Qian Jia (a1) (a2), Ivan Ivanov (a3) (a4), Zlatomir Z. Zlatev (a5), Robert C. Alaniz (a6), Brad R. Weeks (a7), Evelyn S. Callaway (a1), Jennifer S. Goldsby (a1), Laurie A. Davidson (a1) (a4), Yang-Yi Fan (a1) (a2), Lan Zhou (a8), Joanne R. Lupton (a1) (a4), David N. McMurray (a1) (a4) (a6) and Robert S. Chapkin (a1) (a2) (a4)...


Both fish oil (FO) and curcumin have potential as anti-tumour and anti-inflammatory agents. To further explore their combined effects on dextran sodium sulphate (DSS)-induced colitis, C57BL/6 mice were randomised to four diets (2 × 2 design) differing in fatty acid content with or without curcumin supplementation (FO, FO+2 % curcumin, maize oil (control, MO) or MO+2 % curcumin). Mice were exposed to one or two cycles of DSS in the drinking-water to induce either acute or chronic intestinal inflammation, respectively. FO-fed mice exposed to the single-cycle DSS treatment exhibited the highest mortality (40 %, seventeen of forty-three) compared with MO with the lowest mortality (3 %, one of twenty-nine) (P = 0·0008). Addition of curcumin to MO increased (P = 0·003) mortality to 37 % compared with the control. Consistent with animal survival data, following the one- or two-cycle DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared with MO. In contrast, compared with other diets, combined FO and curcumin feeding enhanced the resolution of chronic inflammation and suppressed (P < 0·05) a key inflammatory mediator, NF-κB, in the colon mucosa. Mucosal microarray analysis revealed that dietary FO, curcumin and FO plus curcumin combination differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice
      Available formats


Corresponding author

*Corresponding author: Dr R. S. Chapkin, fax +1 979 862 2378, email


Hide All
1 Mudter, J & Neurath, MF (2003) Mucosal T cells: mediators or guardians of inflammatory bowel disease? Curr Opin Gastroenterol 19, 343349.
2 Yamamoto-Furusho, JK & Podolsky, DK (2007) Innate immunity in inflammatory bowel disease. World J Gastroenterol 13, 55775580.
3 Rubin, DT & Kavitt, RT (2006) Surveillance for cancer and dysplasia in inflammatory bowel disease. Gastroenterol Clin North Am 35, 581604.
4 Davidson, LA, Nguyen, DV, Hokanson, RM, et al. (2004) Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res 64, 67976804.
5 Prescott, SM & Stenson, WF (2005) Fish oil fix. Nature Med 11, 596598.
6 Hudert, CA, Weylandt, KH, Lu, Y, et al. (2006) Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci U S A 103, 1127611281.
7 Chang, WC, Chapkin, RS & Lupton, JR (1997) Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis. Carcinogenesis 18, 721730.
8 Whelan, J & McEntee, MF (2004) Dietary (n-6) PUFA and intestinal tumorigenesis. J Nutr 134, 3421S3426S.
9 Nowak, J, Weylandt, KH, Habbel, P, et al. (2007) Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis 28, 19911995.
10 Hollenbach, E, Vieth, M, Roessner, A, et al. (2005) Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn's disease. J Biol Chem 280, 1498114988.
11 Waetzig, GH, Seegert, D, Rosenstiel, P, et al. (2002) p38 Mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol 168, 53425351.
12 Karrasch, T & Jobin, C (2008) NF-kappaB and the intestine: friend or foe? Inflamm Bowel Dis 14, 114124.
13 Steinbrecher, KA, Harmel-Laws, E, Sitcheran, R, et al. (2008) Loss of epithelial RelA results in deregulated intestinal proliferative/apoptotic homeostasis and susceptibility to inflammation. J Immunol 180, 25882599.
14 Duvoix, A, Blasius, R, Delhalle, S, et al. (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Lett 223, 181190.
15 Deguchi, Y, Andoh, A, Inatomi, O, et al. (2007) Curcumin prevents the development of dextran sulfate sodium (DSS)-induced experimental colitis. Dig Dis Sci 52, 2993–2938.
16 Jian, YT, Mai, GF, Wang, JD, et al. (2005) Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid. World J Gastroenterol 11, 17471752.
17 Camacho-Barquero, L, Villegas, I, Sánchez-Calvo, JM, et al. (2007) Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol 7, 333342.
18 Bharti, AC, Donato, N, Singh, S, et al. (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101, 10531062.
19 Milacic, V, Banerjee, S, Landis-Piwowar, KR, et al. (2008) Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res 68, 72837292.
20 Seril, DN, Liao, J, Yang, GY, et al. (2003) Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 24, 35333562.
21 Xiao, H, Gulen, MF, Qin, J, et al. (2007) The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 26, 461475.
22 Hanai, H & Sugimoto, K (2009) Curcumin has bright prospects for the treatment of inflammatory bowel disease. Curr Pharm Des 15, 20872094.
23 Jia, Q, Lupton, JR, Smith, R, et al. (2008) Reduced colitis-associated colon cancer in fat-1 (n-3 fatty acid desaturase) transgenic mice. Cancer Res 68, 39853991.
24 Hong, MY, Bancroft, LK, Turner, ND, et al. (2005) Fish oil decreases oxidative DNA damage by enhancing apoptosis in rat colon. Nutr Cancer 52, 166175.
25 Ma, DW, Finnell, RH, Davidson, LA, et al. (2005) Folate transport gene inactivation in mice increases sensitivity to colon carcinogenesis. Cancer Res 65, 887897.
26 Kim, W, Fan, YY, Smith, R, et al. (2009) Dietary curcumin and limonin suppress CD4+ T-cell proliferation and interleukin-2 production in mice. J Nutr 139, 10421048.
27 Zlatev, ZZ (2009) zRMicroArray: a computational environment for analyses of gene expression. Masters Thesis, Sofia University, Bulgaria.
28 Strimmer, K (2008) A unified approach to false discovery rate estimation. BMC Bioinformatics 9, 303.
29 Okamoto, R & Watanabe, M (2005) Cellular and molecular mechanisms of the epithelial repair in IBD. Dig Dis Sci 50, Suppl. 1, S34S38.
30 Le Jan, S, Le Meur, N, Cazes, A, et al. (2006) Characterization of the expression of the hypoxia-induced genes neuritin, TXNIP and IGFBP3 in cancer. FEBS Lett 580, 33953400.
31 Kingsbury, GA, Feeney, LA, Nong, Y, et al. (2001) Cloning, expression, and function of BLAME, a novel member of the CD2 family. J Immunol 166, 56755680.
32 Baker, BJ, Akhtar, LN & Benveniste, EN (2009) SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol 30, 392400.
33 Patel, S & Player, MR (2009) Colony-stimulating factor-1 receptor inhibitors for the treatment of cancer and inflammatory disease. Curr Top Med Chem 9, 599610.
34 Ducut Sigala, JL, Bottero, V, Young, DB, et al. (2004) Activation of transcription factor NF-kappaB requires ELKS, an IkappaB kinase regulatory subunit. Science 304, 19631967.
35 Smith, PG, Wilkinson, KN, Savage, KJ, et al. (2005) The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse B-cell lymphoma. Blood 105, 308316.
36 Zhang, R, Maratos-Flier, E & Flier, JS (2009) Reduced adiposity and high-fat diet-induced adipose inflammation in mice deficient for phosphodiesterase 4B. Endocrinology 150, 30763082.
37 Bollrath, J, Phesse, TJ, von Burstin, VA, et al. (2009) gp130-Mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15, 91102.
38 Grivennikov, S, Karin, E, Terzic, J, et al. (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15, 103113.
39 Schraml, BU, Hildner, K, Ise, W, et al. (2009) The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 460, 405409.
40 Kanazawa, S, Tsunoda, T, Onuma, E, et al. (2001) VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation. Am J Gastroenterol 96, 822828.
41 Balla, B, Kósa, JP, Kiss, J, et al. (2009) Transcriptional profiling of immune system-related genes in postmenopausal osteoporotic versus non-osteoporotic human bone tissue. Clin Immunol 131, 354359.
42 Wilson, MD, Cheung, J, Martindale, DW, et al. (2006) Comparative analysis of the paired immunoglobulin-like receptor (PILR) locus in six mammalian genomes: duplication, conversion, and the birth of new genes. Physiol Genomics 27, 201218.
43 Tai, LH, Goulet, ML, Belanger, S, et al. (2008) Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC. J Exp Med 205, 31873199.
44 Funayama, H, Huang, L, Asada, Y, et al. (2010) Enhanced induction of a histamine-forming enzyme, histidine hecarboxylase, in mice primed with nod1 or nod2 ligand in response to various toll-like receptor agonists. Innate Immun 16, 265272.
45 Buac, K, Xu, M, Cronin, J, et al. (2009) NRG1/ERBB3 signaling in melanocyte development and melanoma: inhibition of differentiation and promotion of proliferation. Pigment Cell Melanoma Res 22, 773784.
46 Zou, XH, Jiang, YZ, Zhang, GR, et al. (2009) Specific interactions between human fibroblasts and particular chondroitin sulfate molecules for wound healing. Acta Biomater 5, 15881595.
47 Offenhäuser, N, Borgonovo, A, Disanza, A, et al. (2004) The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway. Mol Biol Cell 15, 9198.
48 Chapkin, RS, McMurray, DN & Lupton, JR (2007) Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol 23, 4854.
49 Hatcher, H, Planalp, R, Cho, J, et al. (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65, 16311652.
50 Weaver, KL, Ivester, P, Seeds, M, et al. (2009) Effect of dietary fatty acids on inflammatory gene expression in healthy humans. J Biol Chem 284, 1540015407.
51 Gurtner, GC, Werner, S, Barrandon, Y, et al. (2008) Wound repair and regeneration. Nature 453, 314321.
52 Blikslager, AT, Moeser, AJ, Gookin, JL, et al. (2007) Restoration of barrier function in injured intestinal mucosa. Physiol Rev 87, 545564.
53 Barrientos, S, Stojadinovic, O, Golinko, MS, et al. (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 16, 585601.
54 Rakoff-Nahoum, S & Medzhitov, R (2007) Prostaglandin-secreting cells: a portable first aid kit for tissue repair. J Clin Invest 117, 8386.
55 Chapkin, RS, Kim, W, Lupton, JR, et al. (2009) Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prostaglandins Leukot Essent Fatty Acids 81, 187191.
56 Koeberle, A, Northoff, H & Werz, O (2009) Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1. Mol Cancer Ther 8, 23482355.
57 Chakravarti, N, Myers, JN & Aggarwal, BB (2006) Targeting constitutive and interleukin-6-inducible signal transducers and activators of transcription 3 pathway in head and neck squamous cell carcinoma cells by curcumin (diferuloylmethane). Int J Cancer 119, 12681275.
58 Courtney, ED, Matthews, S, Finlayson, C, et al. (2007) Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis 22, 765776.
59 Fukata, M, Michelsen, KS, Eri, R, et al. (2005) Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am J Physiol Gastrointest Liver Physiol 288, G1055G1065.
60 Fukata, M, Chen, A, Klepper, A, et al. (2006) Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: role in proliferation and apoptosis in the intestine. Gastroenterology 131, 862877.
61 Rakoff-Nahoum, S & Medzhitov, R (2009) Toll-like receptors and cancer. Nat Rev Cancer 9, 5763.
62 Wong, SW, Kwon, MJ, Choi, AM, et al. (2009) Fatty acids modulate toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a ros-dependent manner. J Biol Chem 284, 2738427392.
63 Huang, S, Zhao, L, Kim, K, et al. (2008) Inhibition of Nod2 signaling and target gene expression by curcumin. Mol Pharmacol 74, 274281.
64 Lee, DY, Lupton, JR, Aukema, HM, et al. (1993) Dietary fat and fiber alter rat colonic mucosal lipid mediators and cell proliferation. J Nutr 123, 18081817.
65 Buchanan, FG & DuBois, RN (2006) Connecting COX-2 and Wnt in cancer. Cancer Cell 9, 68.
66 Hatazawa, R, Tanaka, A, Tanigami, M, et al. (2007) Cyclooxygenase-2/prostaglandin E2 accelerates the healing of gastric ulcers via EP4 receptors. Am J Physiol Gastrointest Liver Physiol 293, G788G797.
67 Ungaro, R, Fukata, M, Hsu, D, et al. (2009) A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis. Am J Physiol Gastrointest Liver Physiol 296, G1167G1179.
68 Fan, YY, Ly, LH, Barhoumi, R, et al. (2004) Dietary docosahexaenoic acid suppresses T cell protein kinase C theta lipid raft recruitment and IL-2 production. J Immunol 173, 61516160.
69 Aggarwal, S, Ichikawa, H, Takada, Y, et al. (2006) Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol 69, 195206.
70 Nishihara, M, Ogura, H, Ueda, N, et al. (2007) IL-6-gp130-STAT3 in T cells directs the development of IL-17+Th with a minimum effect on that of Treg in the steady state. Int Immunol 19, 695702.
71 Wu, S, Rhee, KJ, Albesiano, E, et al. (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15, 10161022.
72 Kortylewski, M, Xin, H, Kujawski, M, et al. (2009) Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 15, 114123.
73 Bouwens, M, van de Rest, O, Dellschaft, N, et al. (2009) Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr 90, 415424.
74 Farzaneh-Far, R, Harris, WS, Garg, S, et al. (2009) Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis 205, 538543.
75 Mähler, M, Bristol, IJ, Leiter, EH, et al. (1998) Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol 274, 3 Pt 1, G544G551.
76 Suzuki, R, Kohno, H, Sugie, S, et al. (2006) Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice. Carcinogenesis 27, 162169.
77 Melgar, S, Karlsson, A & Michaëlsson, E (2005) Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation. Am J Physiol Gastrointest Liver Physiol 288, G1328G1338.
78 Uchiyama, K, Nakamura, M, Odahara, S, et al. (2010) n-3 Polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease. Inflamm Bowel Dis 16, 16961701.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Chapkin Supplementary Material
Chapkin Supplementary Figure 01

 PDF (59 KB)
59 KB
Supplementary materials

Chapkin Supplementary Material
Chapkin Supplementary Figure 02

 PDF (64 KB)
64 KB
Supplementary materials

Chapkin Supplementary Material
Chapkin Supplementary Figure 03

 PDF (113 KB)
113 KB
Supplementary materials

Chapkin Supplementary Material
Chapkin Supplementary Figure 04

 PDF (211 KB)
211 KB
Supplementary materials

Chapkin Supplementary Material
Chapkin Supplementary Figure 05

 PDF (62 KB)
62 KB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed