Synergy between ethanol and grape polyphenols, quercetin, and resveratrol,in the inhibition of the inducible nitric oxide synthase pathway

In atherosclerosis and tumor initiation, inducible nitric oxide synthase (i NOS) has been implicated in the damage of Vascular walls and DNA, respectiv ely. Moderate consumption of red wine has been ascribed as a preventive for coronary heart disease; however, there has been much debate over whether t he beneficial effect is from grape polyphenolic components or ethanol. We s tudied the interaction of grape compounds on nitric oxide (NO) production b y macrophages, mediators of blood vessel damage in atherosclerosis. For the murine macrophage cell line RAW 264.7, stimulation with lipopolysaccharide and interferon-gamma led to expression of the iNOS gene and production of NO. The polyphenols quercetin and resveratrol at a micromolar range suppres sed iNOS gene expression and NO production, as determined by reverse transc ription-polymerase chain reaction and nitrite assay. The polyphenols were a lso found to be scavengers of NO in an acellular system using sodium nitrop russide under physiological conditions. Ethanol, at a moderate level, did n ot produce any appreciable level of reduction of iNOS or NO activity. Howev er, its presence at 0.1 to 0.75% enhanced the effect of grape polyphenols c oncentration-dependently. Thus, the interaction between these components pl ays a significant role in the health effects of red wine, especially with r espect to their effect on the NO pathway. (C) 2000 Elsevier Science Inc.