Inhibitory effect of Zingiber cassumunar extracts on lipopolysaccharide-induced cyclooxygenase-2 and matrix metalloproteinase expression in human gingival fibroblasts

J Periodontal Res. 2013 Aug;48(4):507-16. doi: 10.1111/jre.12033. Epub 2012 Dec 30.

Abstract

Background and 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.

Material and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclooxygenase 1 / drug effects
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Escherichia coli
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Gingiva / cytology
  • Gingiva / drug effects
  • Gingiva / enzymology*
  • Humans
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Kinase 4 / drug effects
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 2 / drug effects*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Phosphorylation
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Zingiberaceae* / chemistry
  • p38 Mitogen-Activated Protein Kinases / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Lipopolysaccharides
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MMP2 protein, human
  • Matrix Metalloproteinase 2