title: ERK1- and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma.
abstract: BACKGROUND
  Dryopteris crassirhizoma Nakai (Aspiadaceae) has been traditionally used as an herbal medicine for treating various inflammatory and infectious diseases such as tapeworm infestation, colds, and viral diseases. However, no systematic studies on the anti-inflammatory actions of Dryopteris crassirhizoma and its inhibitory mechanisms have been reported. We therefore aimed at exploring the anti-inflammatory effects of 95% ethanol extracts (Dc-EE) of this plant.
  
  
  METHODS
  The anti-inflammatory effect of Dc-EE on the production of inflammatory mediators in RAW264.7 cells and HCl/EtOH-induced gastritis was examined. Inhibitory mechanisms were also evaluated by exploring activation of transcription factors, their upstream signalling, and target enzyme activities. Finally, the active components from this extract were also identified using HPLC system.
  
  
  RESULTS
  Dc-EE diminished the production of nitric oxide (NO) and prostaglandin (PG)E(2) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Dc-EE also downregulated the levels of mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by inhibiting the activation of activator protein (AP-1) and IRF3. Indeed, the extract strongly blocked the activities of their upstream kinases ERK1 and TBK1. This extract also strongly ameliorated gastritis symptoms stimulated by HCl/EtOH in mice. According to HPLC fingerprinting, resveratrol, quercetin, and kampferol were identified from Dc-EE.
  
  
  CONCLUSIONS
  Dc-EE displays strong anti-inflammatory activity by suppressing ERK/AP-1 and TBK1/IRF3 pathways, which contribute to its major ethno-pharmacological role as an anti-inflammatory and anti-infectious disease remedy.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Gang Jun
authors.initials: GJ
authors.lastname: Lee
authors.forename: Deok Hyo
authors.initials: DH
authors.lastname: Yoon
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Jueun
authors.initials: J
authors.lastname: Oh
authors.forename: Deok
authors.initials: D
authors.lastname: Jeong
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D032492:Dryopteris; D000431:Ethanol / Q000737:chemistry; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008813:Mice, Inbred ICR; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012997:Solvents; D009569:Nitric Oxide; D000431:Ethanol; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone; D006851:Hydrochloric Acid