Ajoene, a natural product with non-steroidal anti-inflammatory drug (NSAID)-like properties?

Biochem Pharmacol. 2001 Mar 1;61(5):587-93. doi: 10.1016/s0006-2952(00)00580-3.


The inducible isoform of cyclooxygenase (COX-2) is implicated in the pathogenesis of various inflammatory diseases as well as in carcinogenesis, especially of gastrointestinal tumors. Epidemiological as well as experimental data support a role for constituents of allium vegetables, such as garlic and onions, in the prevention of gastrointestinal cancer. Therefore, the aim of the present study was to examine whether the garlic-derived natural product ajoene interferes with the COX-2 pathway by using lipopolysaccharide (LPS)-activated RAW 264.7 cells as in vitro model. Ajoene was shown to dose-dependently inhibit the release of LPS (1 microg/mL)-induced prostaglandin E(2) in RAW 264.7 macrophages (IC(50) value: 2.4 microM). This effect was found to be due to an inhibition of COX-2 enzyme activity by ajoene (IC(50) value: 3.4 microM). Ajoene did not reduce COX-2 expression, but rather increased LPS-induced COX-2 protein and mRNA expression compared to LPS-stimulated cells only. In the absence of LPS, however, ajoene was unable to induce COX-2. The non-steroidal anti-inflammatory drug indomethacin was shown to act similarly in LPS-activated RAW 264.7 cells. These data suggest that ajoene works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs. This finding may add a novel aspect to the biological profile of the garlic-derived natural product ajoene which might be important for understanding the usefulness of garlic for chemoprevention of gastrointestinal carcinomas.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biological Factors / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Disulfides / pharmacology*
  • Isoenzymes / drug effects
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lipopolysaccharides
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / pathology
  • Mice
  • Plant Extracts / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biological Factors
  • Disulfides
  • Isoenzymes
  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • ajoene
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone