title: Oral administration of the flavonoid myricitrin prevents dextran sulfate sodium-induced experimental colitis in mice through modulation of PI3K/Akt signaling pathway.
abstract: METHODS
  We investigated the protective effect of the flavonoid myricitrin in dextran sulfate sodium (DSS) induced colitis as promising candidate for the treatment of ulcerative colitis which is considered an important worldwide public health problem.
  
  
  RESULTS
  Male CD1 mice were provided with a solution of filtered water containing 3% w/v DSS ad libitum over a 5-day period followed by 2 days with normal drinking water. Myricitrin was administered orally, once a day, at the doses 1, 3, and 10 mg/kg of body weight. At the end of day 7th, the animals were euthanized and the colonic tissue was collected to be analyzed by RT-PCR, immunohistochemistry and Western blot. Our results showed that oral treatment with myricitrin exerts consistent anti-inflammatory action in DSS-induced acute colitis in mice by the inhibition of the Akt/phosphatidylinositol-3 kinase-dependent phosphorylation. Consequently, the phosphorylation of mitogen-activated protein kinases (MAPK) p38, extracellular signal-regulated protein kinase (ERK1/2), and c-Jun N-terminal kinase and of the nuclear factor B (NF-κB) was reduced and prevented an increase in the cytokines/chemokines levels.
  
  
  CONCLUSIONS
  Together, these data reveal that the anti-inflammatory effect of myricitrin in DSS-induced colitis in mice is likely associated with its ability to prevent the activation of upstream kinases, such as phosphatidylinositol-3 kinase-dependent Akt, NF-κB, and mitogen-activated protein kinase.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Raquel Cristina
authors.initials: RC
authors.lastname: Schwanke
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Marcon
authors.forename: Flavia Carla
authors.initials: FC
authors.lastname: Meotti
authors.forename: Allisson Freire
authors.initials: AF
authors.lastname: Bento
authors.forename: Rafael Cypriano
authors.initials: RC
authors.lastname: Dutra
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzollatti
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D005419:Flavonoids; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C008577:myricitrin; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; C497256:Prkce protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D051744:Protein Kinase C-epsilon; D048051:p38 Mitogen-Activated Protein Kinases
keywords: DSS-induced colitis; MAPK; Myricitrin; NF-κB; PI3K/Akt pathway