Ajoene, a natural product with non-steroidal anti-inflammatory drug (NSAID)-like properties?
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.
Dirsch
V M
VM
Institute of Pharmacy, Center of Drug Research, Butenandtstrasse 5-13 B, University of Munich, 81377, Munich, Germany. Verena.Dirsch@cup.uni-muenchen.de
Vollmar
A M
AM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001685:Biological Factors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013454:Sulfoxides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001685:Biological Factors; D004220:Disulfides; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; D013454:Sulfoxides; C048980:ajoene; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone