Curcumin attenuates DNB-induced murine colitis.
Numerous therapies used for inflammatory bowel disease (IBD) target the transcription factor NF-kappaB, which is involved in the production of cytokines and chemokines integral for inflammation. Here we show that curcumin, a component of the spice turmeric, is able to attenuate colitis in the dinitrobenzene sulfonic acid (DNB)-induced murine model of colitis. When given before the induction of colitis it reduced macroscopic damage scores and NF-kappaB activation. This was accompanied by a reduction in myeloperoxidase activity, and using semiquantitative RT-PCR, an attenuation of the DNB-induced message for IL-1beta was detected. Western blotting analysis revealed that there was a reproducible DNB-induced activation of p38 MAPK detected in intestinal lysates by using a phosphospecific antibody. This signal was significantly attenuated by curcumin. Furthermore, we show that the immunohistochemical signal is dramatically attenuated at the level of the mucosa by curcumin. We conclude that the widely used food additive curcumin is able to attenuate experimental colitis through a mechanism correlated with the inhibition of the activation of NF-kappaB and effects a reduction in the activity of p38 MAPK. We propose that this agent may have therapeutic implications for human IBD.
Salh
B
B
Jack Bell Research Centre, Children and Women's Hospital, Vancouver, BC, Canada V5Z 3P1.
Assi
K
K
Templeman
V
V
Parhar
K
K
Owen
D
D
Gómez-Muñoz
A
A
Jacobson
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001557:Benzenesulfonates; D015415:Biomarkers; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001557:Benzenesulfonates; D015415:Biomarkers; D016328:NF-kappa B; C007488:dinitrobenzenesulfonic acid; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin