Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway
Section snippets
Materials
Quercetin, resveratrol, MTT, and SNP were purchased from the Sigma Chemical Co. The murine macrophage cell line RAW 264.7 was obtained from the American Type Culture Collection. The macrophages were cultured in RPMI-1640 medium containing 100 U/mL of penicillin, 100 μg/mL of streptomycin, 2 mM glutamine, 0.01 mM sodium pyruvate, 0.1 mM nonessential amino acids, 0.05 mM 2-mercaptoethanol, and 10% fetal bovine serum. RPMI-1640 and other tissue culture reagents were from Life Technologies, except
Synergy between ethanol and quercetin or resveratrol in inhibiting NO production of stimulated macrophages
In the presence of 1% ethanol, quercetin, from 3 to 100 μM, reduced NO production in a concentration-dependent manner by 21.8 to 99% (Fig. 1). The ic50 value was 7.6 μM. To examine the synergism between ethanol and quercetin, ethanol was decreased further, titrating from 0.75 to 0.1%. A concentration of 30 μM was at the log phase of the quercetin inhibition curve when 0.1% ethanol was added, and thus was selected to study whether ethanol increases the efficacy of polyphenol (data not shown).
Discussion
Alcohol is the major component of wine. Whether ethanol or grape polyphenols confer the health benefits of red wine has been a subject of much debate. Many favor one component over another; however, few have looked for interactions between the components. In this report, we have shown that ethanol acts in synergy with quercetin and resveratrol. We have found that the grape polyphenols inhibit iNOS-mediated NO production of stimulated murine macrophages more effectively when given in increasing
Acknowledgements
The authors would like to thank Drs. Robert Herman and Linda Romagnano for reading the manuscript. This study was supported, in part, by a grant from the Temple University School of Podiatric Medicine
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2018, Studies in Natural Products ChemistryCitation Excerpt :Accumulation of resveratrol in organs such as heart, liver, and lungs was first described in 1996 [86], was recently confirmed [94], and the list was extended to include bile, stomach, and kidney [95]. A synergic action of resveratrol was found with quercetin and ellagic acid in inducing apoptosis in human leukemic cells [96], with ethanol in the inhibition of iNOS expression [97], with vitamin D [98], with vitamin E in the prevention of lipid peroxidation [99], with catechin in the protection of PC12 cells against β-amyloid toxicity [100], with nucleoside analogs in the inhibition of HIV1 replication in cultured T lymphocytes [101], and with tyrosol and β-sitosterol in the modulation of LDL oxidative stress and synthesis of PGE2 [102]. Investigation of the bioavailability and pharmacokinetics of resveratrol and its analog pterostilbene showed that the latter compound had a higher biological activity in vivo [103].