Heme oxygenase-1-mediated anti-inflammatory effect of a novel garlic compound in RAW264.7 murine macrophages

This study investigated the effects of (10Z)-1-[(5Z,8Z)-tetradeca-5,8-dienoyloxy]-3-[(Z)-tetradec-8-enoyloxy]propan-2-yl hexadec-10-enoate (TTPH) from garlic on the inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) systems in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The TTPH dose-dependently reduced nitrite accumulation and production of prostaglandin E2 in the supernatants of LPS-stimulated macrophages. Markedly reduced iNOS and COX-2 enzyme activities were observed in Western blots. In addition, a dose-dependent change in mRNA expression was recorded using reverse transcription-polymerase chain reaction analyses. Moreover, TTPH exerted antiinflammatory activity by inducing heme oxygenase-1 (HO-1) expression; this was supported by the use of the HO-1 inhibitor protoporphyrin IX, which abolished the inhibitory effect of TTPH on the production of nitric oxide, tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 in LPS-stimulated macrophages. These observations indicate that TTPH inhibits the expression of iNOS and COX-2, and up-regulates HO-1 in activated macrophages. The possible link of this effect to the beneficial features attributed to garlic is discussed.