Abstract
Polyphenols (PPH) represent a group of chemical substances found in plants, characterized by the presence of more than one phenol unit. The largest and best studied polyphenols are the flavonoids. Polyphenols contained in red wine have beneficial effects on cardiovascular health. The aim of our research was a comparative and interactive study of four red wine polyphenols - resveratrol (R), quercetin (Q), kaempferol (K) and isorhamnetin (IH) which may have a long term properties as the increase of nitric oxide (NO) synthase expression, acting on the prometer activity when used alone or in equimolar mixtures. To determine their activity, we performed a luciferase reporter gene assay on EA.hy926 cells stably transfected with a luciferase reporter gene construct containing eNOS promoter. The Bradford assay was also performed to evaluate the cytotoxicity and the differences in cell number. The median effect equation, as an interaction analysis evaluating synergy or antagonism of the combinations was done according to the principle of mass-action law and the dose reduction index (DRI) was calculated for all mixtures. All single polyphenols activated eNOS promoter. The EC50 values were in micromolar concentrations ranging from 3.44 µM (R2 = 0.96) for kaempferol to 9.89 µM for isorhamnetin (R2 = 0.94). All mixtures activated eNOS promoter, but their interactions varied from synergy (Q+R, Q+IH+K, Q+R+K and Q+R+IH+K), through additive (R+IH+K) to antagonistic interaction (R+IH, R+K, Q+IH, Q+K, IH+K and R+Q+IH). In this study, we show for the first time that red wine polyphenols activated eNOS promoter when used alone and in mixtures with different types of interactions. Key words: Polyphenols, eNOS promoter, luciferase reporter gene assay, interaction analysis.
Highlights
Growing interest in a polyphenol rich diet has been observed in recent years
Recent studies have demonstrated that polyphenols such as resveratrol, quercetin, epigallocatechin-3-gallate and delphinidin enhance nitric oxide (NO) output to improve endotheliumdependent vascular relaxation Moderate regular red wine consumption is associated with a reduced risk of cardiovascular diseases and is related with activation of endothelial nitric oxide synthase (eNOS) system at different levels
All polyphenols activated eNOS promoter, the EC50 values were in micromolar concentration ranging from 3.44 μM (R2 = 0.95) for kaempferol to 9.89 μM for isorhamnetin (R2 = 0.94) (Table 1)
Summary
Growing interest in a polyphenol rich diet has been observed in recent years. It is believed that they can protect against various diseases, e.g. cancers, cardiovascular diseases, diabetes, and some immunological disorders (Haysteen, 2002; Xia et al, 2010). Polyphenols can counteract ROS as well as modulate signaling pathways to enhance health outcomes in the realm of cardiovascular disorders and aging. They play a key role of Reactive Oxygen Species in Disease (Sandhya et al, 2013). Recent studies have demonstrated that polyphenols such as resveratrol, quercetin, epigallocatechin-3-gallate and delphinidin enhance NO output to improve endotheliumdependent vascular relaxation Moderate regular red wine consumption is associated with a reduced risk of cardiovascular diseases and is related with activation of eNOS system at different levels. Moderate ethanol intake from any type of beverage improves lipoprotein metabolism and, lowers cardiovascular mortality risk, but wine, red wine with its abundant content of phenolic acids, polyphenols, and flavonoids seems to confer additional health benefits
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