The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function

Abstract

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.

Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials

“…Furthermore, it has been reported that lipid accumulation and mRNA expression of FAS and SREBP1-c in 3T3-L1 adipocytes were decreased when treated with cyanidin rather than malvidin [21], and the inhibitory effects of anthocyanidins on α-glucosidase were in the order of delphinidin > cyanidin > malvidin [68]. In a study by Aboufarrag et al, gallic acid, a delphinidin-3-glucoside metabolite, increased the lactonase activity of PON1 R192R phenotypes significantly, which did not change with PCA, a cyanidin-3-glucoside metabolite, or syringic acid, a malvidin-3-glucoside metabolite [69].…”

Nutraceutical Activity of Anthocyanins from the Edible Berries of Rhamnus pompana

“…[5,6] It is known that anthocyanin ingesting may influence paraoxonase 1 (PON1) activity which is essentially regulated by diet and genetic polymorphisms. [7] This fact strongly suggest that genetics may also influence the metabolism of antioxidants, including anthocyanins. In this context, local plant foods are envisioned as natural sources of nutraceuticals with potential benefits for native people who regularly consume it.…”

“…Interestingly, remarkable correlations have been observed in the consumption rate of anthocyanins with overweight prevention in populations from the Middle East, Asia, Europe, South America, and Oceania [5,6] . It is known that anthocyanin ingesting may influence paraoxonase 1 (PON1) activity which is essentially regulated by diet and genetic polymorphisms [7] . This fact strongly suggest that genetics may also influence the metabolism of antioxidants, including anthocyanins.…”

Tackling Atherosclerosis via Selected Nutrition

“…In [ 270 ] the ability of ethylpyruvate to inhibit LDL oxidation on human vascular endothelial cells, EA.hy926, was evaluated. In the work H.T., The effect of anthocyanins on the expression of the PON1 gene was studied on a Huh7 liver hepatoma cell culture [ 271 ]. In [ 266 ] it has been shown that studies are often carried out on liver HepG2 cells, intestinal Caco2 cells, and 3LT3 adipocyte cells.…”