Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells

Life Sci. 2003 Jun 6;73(3):337-48. doi: 10.1016/s0024-3205(03)00288-1.

Abstract

Inducible cyclooxygenase (COX-2) has been implicated in the processes of inflammation and carcinogenesis. Thus, the potential COX-2 inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. In this study, the methanolic extract of the cortex of Eugenia caryophyllata Thunberg (Myrtaceae) was found to potently inhibit the prostaglandin E(2) production in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells (98.3% inhibition at the test concentration of 10 microg/ml). Further, hexane-soluble layer was the most active partition compared to ethyl acetate, n-butanol, and water-soluble parts. By bioassay-guided fractionation of hexane-soluble partition, eugenol was isolated and exhibited a significant inhibition of PGE(2) production (IC(50) = 0.37 microM). In addition, eugenol suppressed the cyclooxygenase-2 (COX-2) gene expression in LPS-stimulated mouse macrophage cells. On the line of COX-2 playing an important role in colon carcinogenesis further study was designed to investigate the effect of eugenol on the growth and COX-2 expression in HT-29 human colon cancer cells. Eugenol inhibited the proliferation of HT-29 cells and the mRNA expression of COX-2, but not COX-1. This result suggests that eugenol might be a plausible lead candidate for further developing the COX-2 inhibitor as an anti-inflammatory or cancer chemopreventive agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / isolation & purification
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / toxicity
  • Dinoprostone / biosynthesis
  • Eugenol / isolation & purification
  • Eugenol / pharmacology*
  • Eugenol / toxicity
  • Gene Expression Regulation, Enzymologic / drug effects
  • HT29 Cells
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / genetics
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Membrane Proteins
  • Mice
  • Plant Extracts / chemistry
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Syzygium / chemistry*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Plant Extracts
  • RNA, Messenger
  • lipopolysaccharide, Escherichia coli O111 B4
  • Eugenol
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone