title: A combined omics approach to evaluate the effects of dietary curcumin on colon inflammation in the Mdr1a(-/-) mouse model of inflammatory bowel disease.
abstract: The aim of this study was to provide insight into how curcumin reduces colon inflammation in the Mdr1a(-/-) mouse model of human inflammatory bowel disease using a combined transcriptomics and proteomics approach. Mdr1a(-/-) and FVB control mice were randomly assigned to an AIN-76A (control) diet or AIN-76A+0.2% curcumin. At 21 or 24weeks of age, colonic histological injury score (HIS) was determined, colon mRNA transcript levels were assessed using microarrays and colon protein expression was measured using 2D gel electrophoresis and LCMS protein identification. Colonic HIS of Mdr1a(-/-) mice fed the AIN-76A diet was higher (P<.001) than FVB mice fed the same diet; the curcumin-supplemented diet reduced colonic HIS (P<.05) in Mdr1a(-/-) mice. Microarray and proteomics analyses combined with new data analysis tools, such as the Ingenuity Pathways Analysis regulator effects analysis, showed that curcumin's antiinflammatory activity in Mdr1a(-/-) mouse colon may be mediated by activation of α-catenin, which has not previously been reported. We also show evidence to support curcumin's action via multiple molecular pathways including reduced immune response, increased xenobiotic metabolism, resolution of inflammation through decreased neutrophil migration and increased barrier remodeling. Key transcription factors and other regulatory molecules (ERK, FN1, TNFSF12 and PI3K complex) activated in inflammation were down-regulated by dietary intervention with curcumin.
authors.affiliation: Biological Chemistry & Bioactives Group and Food Innovation, Plant & Food Research, Hamilton 3240, New Zealand.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Cooney
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, Palmerston North 4442, New Zealand; GRAVIDA: National Centre for Growth and Development, Auckland 1142, New Zealand. Electronic address: matthew.barnett@agresearch.co.nz.
authors.forename: Matthew P G
authors.initials: MP
authors.lastname: Barnett
authors.affiliation: Food and Nutrition, Food Innovation, Plant & Food Research, Palmerston North 4442, New Zealand.
authors.forename: Yvonne E M
authors.initials: YE
authors.lastname: Dommels
authors.affiliation: Biological Chemistry & Bioactives Group and Food Innovation, Plant & Food Research, Auckland 1025, New Zealand.
authors.forename: Diane
authors.initials: D
authors.lastname: Brewster
authors.affiliation: Food and Nutrition, Food Innovation, Plant & Food Research, Palmerston North 4442, New Zealand.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Butts
authors.affiliation: AgResearch, Palmerston North 4442, New Zealand; Riddet Institute, Massey University, Palmerston North 4474, New Zealand.
authors.forename: Warren C
authors.initials: WC
authors.lastname: McNabb
authors.affiliation: Biological Chemistry & Bioactives Group and Food Innovation, Plant & Food Research, Auckland 1025, New Zealand.
authors.forename: William A
authors.initials: WA
authors.lastname: Laing
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, Palmerston North 4442, New Zealand; GRAVIDA: National Centre for Growth and Development, Auckland 1142, New Zealand; Riddet Institute, Massey University, Palmerston North 4474, New Zealand.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Roy
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000818:Animals; D003092:Colitis / Q000517:prevention & control*; D003474:Curcumin / Q000008:administration & dosage*; D004032:Diet; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D051379:Mice; D008958:Models, Molecular
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C095122:multidrug resistance protein 3; D003474:Curcumin
keywords: Alpha catenin; Curcuma longa; Extracellular matrix; Oligonucleotide array sequence analysis; Two-dimensional difference gel electrophoresis