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

• Published in: Biochemical pharmacology Vol. 60; no. 10; pp. 1539 - 1548
• Main Authors: Man-Ying Chan, Marion, Mattiacci, John A, Hwang, Hyon S, Shah, Amit, Fong, Dunne
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.2000; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Cell metabolism, cell oxidation; Cell physiology; Cells, Cultured; Drug Synergism; Enzyme Inhibitors - pharmacology; ethanol; Ethanol - pharmacology; Flavonoids; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; inducible nitric oxide synthase; macrophages; Macrophages - drug effects; Macrophages - metabolism; Mice; Molecular and cellular biology; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II; Phenols - pharmacology; Polymers - pharmacology; quercetin; Quercetin - pharmacology; Resveratrol; Rosales - chemistry; Stilbenes - pharmacology; quercetin; macrophages; nitric oxide; resveratrol; ethanol; inducible nitric oxide synthase; Synergism; Polyphenol; Enzymatic activity; Established cell line; Solvent; Chemical association; Ethanol; Enzyme; Rodentia; Enzyme inhibitor; Gene expression; In vitro; Radical scavenger; Biological activity; Nitric-oxide synthase; Vertebrata; Mammalia; Mouse; Animal; Nitric oxide; Grape; Plant origin; Quercetin; Oxidoreductases; Macrophage
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(00)00471-8

In atherosclerosis and tumor initiation, inducible nitric oxide synthase (iNOS) has been implicated in the damage of vascular walls and DNA, respectively. Moderate consumption of red wine has been ascribed as a preventive for coronary heart disease; however, there has been much debate over whether the beneficial effect is from grape polyphenolic components or ethanol. We studied the interaction of grape compounds on nitric oxide (NO) production by macrophages, mediators of blood vessel damage in atherosclerosis. For the murine macrophage cell line RAW 264.7, stimulation with lipopolysaccharide and interferon-γ led to expression of the iNOS gene and production of NO. The polyphenols quercetin and resveratrol at a micromolar range suppressed iNOS gene expression and NO production, as determined by reverse transcription–polymerase chain reaction and nitrite assay. The polyphenols were also found to be scavengers of NO in an acellular system using sodium nitroprusside under physiological conditions. Ethanol, at a moderate level, did not produce any appreciable level of reduction of iNOS or NO activity. However, its presence at 0.1 to 0.75% enhanced the effect of grape polyphenols concentration-dependently. Thus, the interaction between these components plays a significant role in the health effects of red wine, especially with respect to their effect on the NO pathway.