title: Reactive oxygen species removal activity of davallialactone reduces lipopolysaccharide-induced pulpal inflammation through inhibition of the extracellular signal-regulated kinase 1/2 and nuclear factor kappa b pathway.
abstract: BACKGROUND
  Davallialactone, hispidin analogues derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study examined whether the reactive oxygen species (ROS) removal activity of davallialactone affects the lipopolysaccharide (LPS)-induced anti-inflammatory activity in human dental pulp cells.
  
  
  METHODS
  The LPS-induced formation of ROS was analyzed by using dichlorofluorescein diacetate with fluorescence-activated cell sorter, and the expression of inflammatory molecules in primary cultured human dental pulp cells was determined by immunoblotting. The inflammatory mechanism of the davallialactone-involved signal pathway was examined by immunoblotting.
  
  
  RESULTS
  Davallialactone acted as an antioxidant to confirm the elimination of ROS formation and elevation of Cu/Zn superoxide dismutase and Mn superoxide dismutase expression in LPS-induced pulp cells. The antioxidant activity of davallialactone leads to inhibition of LPS-induced inflammation by blocking the extracellular signal-regulated kinase (ERK1/2) and nuclear factor kappa B (NF-κB) pathway, which decreases the expression of inflammatory molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, matrix metalloproteinase-2, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclooxygenase-2. The character of davallialactone was more effective in comparison with N-acetylcysteine as the control antioxidant in this study.
  
  
  CONCLUSIONS
  Davallialactone has antioxidant activity and anti-inflammatory effects in LPS-induced human dental pulp cells through the suppression of ERK1/2 activation followed by blockage of NF-κB translocation from cytosol into nuclear. Therefore, the good anti-inflammatory capacity of davallialactone might be used for oral diseases such as pulpitis and periodontitis.
authors.affiliation: Department of Oral Biochemistry, School of Medicine, Chonbuk National University, Jeonju, Korea.
authors.forename: Nan-Hee
authors.initials: NH
authors.lastname: Lee
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Govinda
authors.initials: G
authors.lastname: Bhattari
authors.forename: In-Kyoung
authors.initials: IK
authors.lastname: Lee
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Jae-Gyu
authors.initials: JG
authors.lastname: Jeon
authors.forename: Pyong-Han
authors.initials: PH
authors.lastname: Hwang
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D011671:Pulpitis / Q000473:pathology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D007783:Lactones; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C068766:davallialactone; C029569:diacetyldichlorofluorescein; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D000111:Acetylcysteine