title: Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is a major source of morbidity in children and adults. Its incidence is rising, particularly in young people. IBD carries a lifelong risk of cancer, which is proportional to disease duration. Drug and surgical treatments rarely offer cure and often carry a high side effect burden. Dietary therapy is highly effective in Crohn's disease. For these reasons, there is much interest in developing novel dietary treatments in IBD. Curcumin, a component of the spice turmeric, and an anti-inflammatory and anti-cancer agent, shows preclinical and clinical potential in IBD. Its mechanisms of action are unknown. Our aim was to assess the effect of curcumin on key disease mediators p38 mitogen-activated protein kinase (MAPK), IL-1beta, IL-10 and matrix metalloproteinase-3 (MMP-3) in the gut of children and adults with IBD. Colonic mucosal biopsies and colonic myofibroblasts (CMF) from children and adults with active IBD were cultured ex vivo with curcumin. p38 MAPK, NF-kappaB and MMP-3 were measured by immunoblotting. IL-1beta and IL-10 were measured by ELISA. We show reduced p38 MAPK activation in curcumin-treated mucosal biopsies, enhanced IL-10 and reduced IL-1beta. We demonstrate dose-dependent suppression of MMP-3 in CMF with curcumin. We conclude that curcumin, a naturally occurring food substance with no known human toxicity, holds promise as a novel therapy in IBD.
authors.affiliation: Centre for Digestive Diseases, Institute of Cell and Molecular Science, Barts and the London School of Medicine, Queen Mary, University of London, London E1 2AT, UK. j.epstein@qmul.ac.uk
authors.forename: Jenny
authors.initials: J
authors.lastname: Epstein
authors.forename: Guillermo
authors.initials: G
authors.lastname: Docena
authors.forename: Thomas T
authors.initials: TT
authors.lastname: MacDonald
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sanderson
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000293:Adolescent; D001706:Biopsy; D002648:Child; D003106:Colon; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis*; D053583:Interleukin-1beta / Q000032:analysis*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D003474:Curcumin