Abstract

Recently, we demonstrated that the consumption of a bolus of bilberry extract modulates the transcription of Nrf2-regulated genes in peripheral blood lymphocytes (PBL) of healthy volunteers, accompanied by decreased DNA-damage. In the present study, we addressed the question whether consumption of consumer-relevant amounts of anthocyanin-rich beverages can achieve similar effects. The impact of three different anthocyanin-rich beverages on Nrf2-dependent gene transcription as well as and the status of DNA-damage in whole blood was investigated. After a polyphenol-reduced diet, five healthy male subjects consumed a bolus (700 mL) of respective test beverages with blood sampling up to 8 h after intake. All beverages affected the transcription of Nrf2, HO-1 and NQO-1, but showed different potencies and persistence of effects. Consumption of red fruit juice significantly reduced total DNA strand breaks (with formamidopyrimidine-DNA-glycosylase-(fpg) treatment) after 8 h in blood samples of the volunteers, suggesting antioxidant and DNA protective effects, albeit transcript levels of Nrf2-dependent genes had reached the basal state. The amount of basic DNA strand breaks (damage without oxidative DNA strand breaks) remained unchanged during the monitoring period. In contrast, a beverage prepared from grape skin extract significantly increased basic and total DNA strand breaks 2 h after intake, underlining the necessity of further investigations regarding composition, safety and consumer´s acceptance of respective products to exclude undesired adverse effects. Consumption of a bolus of anthocyanin-rich beverages affected Nrf2 and Nrf2-dependent gene transcription in human PBL and DNA integrity, which is indicative for systemic effects.

Highlights

  • A misbalance in the homeostasis of reactive oxygen species (ROS) is known to contribute to the pathogenesis of a spectrum of life-style and nutrition-associated chronic diseases [1]

  • In a human pilot intervention study, we demonstrated recently that the consumption of a bolus of bilberry extract modulates the transcription of Nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) in peripheral blood lymphocytes (PBL) of the volunteers, accompanied by a decrease of total Deoxyribonucleic acid (DNA) damage [6]

  • In the present pilot intervention study, we addressed the question whether induction of Nrf2-dependent gene expression and a respective decrease of DNA damage are only possible with highly concentrated extracts or whether already a single bolus of consumer-relevant anthocyanin-rich juice is sufficient to achieve a significant modulation of the Nrf2-dependent protective system

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Summary

Introduction

A misbalance in the homeostasis of reactive oxygen species (ROS) is known to contribute to the pathogenesis of a spectrum of life-style and nutrition-associated chronic diseases [1]. After binding to small-Maf proteins (sMaf ), the resulting complex binds to antioxidant responsive elements (ARE), regulating the transcription of a battery of genes including important phase-II-enzymes as well as enzymes crucial for antioxidant defense like NQO-1 and HO-1 [2, 13,14,15,16]. In a human pilot intervention study, we demonstrated recently that the consumption of a bolus of bilberry extract modulates the transcription of Nrf, NQO-1 and HO-1 in peripheral blood lymphocytes (PBL) of the volunteers, accompanied by a decrease of total DNA damage [6]. A significant reduction of basic and total DNA strand breaks was reported in a human intervention study with healthy male volunteers after 4 weeks’ consumption of 700 mL anthocyanin-rich fruit juice [9]. In the latter study only the impact on DNA integrity in the PBL of the volunteers was monitored, leaving open the question if the observed effects are associated with an impact on the Nrf2-pathway

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