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

The inducible isoform of cyclooxygenase (COX-2) is implicated in the pathog enesis of various inflammatory diseases as well as in carcinogenesis, espec ially of gastrointestinal tumors. Epidemiological as well as experimental d ata support a role for constituents of allium vegetables, such as garlic an d onions, in the prevention of gastrointestinal cancer. Therefore, the aim of the present study was to examine whether the garlic-derived natural prod uct ajoene interferes with the COX-2 pathway by using lipopolysaccharide (L PS)-activated RAW 264.7 cells as in vitro model. Ajoene was shown to dose-d ependently inhibit the release of LPS (1 mug/mL)-induced prostaglandin E-2 in RAW 264.7 macrophages (IC50 value: 2.3 muM). This effect was found to be due to an inhibition of COX-2 enzyme activity by ajoene (IC50 value: 3.4 m uM). Ajoene did not reduce COX-2 expression, but rather increased LPS-induc ed 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 i n 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-inflam matory 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 gastrointesti nal carcinomas. (C) 2001 Elsevier Science Inc. All rights reserved.