title: Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.
abstract: This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas.
authors.forename: Hyemee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program of Toxicology, Texas A&M University, College Station, Texas.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Banerjee
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Barnes
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Pfent
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Talcott
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas.|Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas.|Department of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas.|Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas.|Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas.
authors.forename: Susanne U
authors.initials: SU
authors.lastname: Mertens-Talcott
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000067030:Fruit and Vegetable Juices / Q000032:analysis; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D031022:Mangifera / Q000737:chemistry; D035683:MicroRNAs / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D059808:Polyphenols / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C527111:MIRN126 microRNA, human
keywords: colitis; mTOR; mango; miR-126; rat