EFFECT OF ALLICIN AND AJOENE, 2 COMPOUNDS OF GARLIC, ON INDUCIBLE NITRIC-OXIDE SYNTHASE

Inducible nitric oxide synthase (iNOS) has recently been shown to be p resent in human atherosclerotic lesions and to promote the formation o f deleterious peroxynitrite. Allicin and ajoene are discussed as activ e compounds with regard to the beneficial effects of garlic in atheros clerosis. The aim of this study was to investigate the effect of allic in and ajoene on the iNOS system in lipopolysaccharide (LPS)-stimulate d RAW 264.7 macrophages. Ajoene (IC50 2.5-5 mu M) and allicin (IC50 15 -20 mu M) dose dependently reduced nitrite accumulation, a parameter f or NO synthesis, in supernatants of LPS-stimulated (1 mu g/ml, 20 h) m acrophages. Accordingly, reduced iNOS enzyme activities were measured by conversion of L-[H-3]arginine to L-[H-3]citrulline in homogenates o f LPS-activated cells treated with ajoene or allicin. None of these co mpounds, however, showed a direct effect on the catalytic activity of iNOS. Consequently, iNOS protein and mRNA expression in ajoene (10 mu M) or allicin (50 mu M) treated cells were evaluated by Western blot a nd Northern blot analysis, respectively. Markedly reduced iNOS protein as well as mRNA levels were demonstrated. These observations indicate that allicin and ajoene inhibit the expression of iNOS in activated m acrophages. The possible link of this effect to the beneficial feature s attributed to garlic is discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.