title: Inhibitory effect of Zingiber cassumunar extracts on lipopolysaccharide-induced cyclooxygenase-2 and matrix metalloproteinase expression in human gingival fibroblasts.
abstract: OBJECTIVE
  Lipopolysaccharides (LPS) induce the production of proinflammatory mediators such as prostaglandins and matrix metalloproteinases (MMPs) in human gingival fibroblasts (HGFs). Zingiber cassumunar is a medicinal plant that possesses anti-inflammatory properties. The aim of this study was to determine the effects of the Z. cassumunar extract on the expression of cyclooxygenase (COX)-1, COX-2 and MMP-2 in HGFs challenged with LPS.
  
  
  METHODS
  HGFs were treated with LPS in the presence or absence of Z. cassumunar extracts. The levels of expression of COX-1, COX-2 and MMP-2 mRNAs and of COX-1, COX-2 and MMP-2 proteins were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. MMP-2 activities in cell-culture supernatants were determined using gelatin zymography. MAPK activation was evaluated by western blotting.
  
  
  RESULTS
  LPS treatment of HGFs resulted in the activation of ERK1/2, p38 and JNK. Z. cassumunar extracts significantly inhibited the phosphorylation of ERK1/2 and JNK in HGFs stimulated with LPS. A lesser inhibitory effect was observed for the phosphorylation of p38. RT-PCR and western blot analyses showed that Z. cassumunar extracts inhibited the LPS-induced expression of COX-2 mRNA and COX-2 protein, respectively, but not of COX-1 mRNA or COX-1 protein. Pretreatment of HGFs with Z. cassumunar also attenuated the induction of MMP-2 with LPS.
  
  
  CONCLUSIONS
  Our results indicate that Z. cassumunar extracts inhibit COX-2 and MMP-2 production by LPS-activated human gingival fibroblasts through blocking the proinflammatory signaling pathway involving ERK1/2, JNK and p38.
authors.affiliation: Oral Biology Laboratory, Faculty of Dentistry, Thammasat University, Klong Luang, Prathumthani, Thailand. koontongkaew@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Koontongkaew
authors.forename: L
authors.initials: L
authors.lastname: Meesuk
authors.forename: V
authors.initials: V
authors.lastname: Aupaphong
authors.forename: T Dechatiwongse Na
authors.initials: TD
authors.lastname: Ayudhaya
authors.forename: O
authors.initials: O
authors.lastname: Poachanukoon
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D030521:Zingiberaceae / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2