Effect of Coffee Combining Green Coffee Bean Constituents with Typical Roasting Products on the Nrf2/ARE Pathway in Vitro and in Vivo

Abstract

This study investigated Nrf2-activating properties of a coffee blend combining raw coffee bean constituents with 5-O-caffeoylquinic acid (CGA) as a lead component with typical roasting products such as N-methylpyridinium (NMP). In cell culture (HT29) the respective coffee extract (CN-CE) increased nuclear Nrf2 translocation and enhanced the transcription of ARE-dependent genes as exemplified for NAD(P)H:quinone oxidoreductase and glutathione-S-transferase (GST)A1, reflected in the protein level by an increase in GST enzyme activity. In a pilot human intervention study (29 healthy volunteers), daily consumption of 750 mL of CN-coffee for 4 weeks increased Nrf2 transcription in peripheral blood lymphocytes on average. However, the transcriptional response pattern of Nrf2/ARE-dependent genes showed substantial interindividual variations. The presence of SNPs in the Nrf2-promoter, reported recently, as well as the detection of GSTT1*0 (null) genotypes in the study collective strengthens the hypothesis that coffee acts as a modulator of Nrf2-dependent gene response in humans, but genetic polymorphisms play an important role in the individual response pattern.

Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction

“…We previously reported that several CQAs are present in CAW and can protect against Aβ cytotoxicity [22]. CQAs have also been shown to affect mitochondrial function and to possess antioxidant activity in primary neurons as well as neuronal cell lines [47–49]. In this study we evaluated two CQAs, present at the highest concentrations in CAW [22] to determine if they mediate the effects of the complete extract.…”

Cardiometabolic effects of two coffee blends differing in content for major constituents in overweight adults: a randomized controlled trial

“…This hypothesis is supported by results from a pilot study with 29 healthy volunteers, where after daily consumption of 750 ml coffee for 4 weeks, an increased Nrf2 transcription in peripheral blood lymphocytes had been observed. However, the transcriptional response pattern of Nrf2/ARE-dependent genes showed substantial inter-individual variations according to single nucleotide polymorphisms (SNPs) in the Nrf2-promoter, which seem to play an important role in the individual response pattern [29,30]. Therefore, we could not exclude for our trial that such gene polymorphisms could have disguised potential effects of coffee on weight regulation.…”

Relationship between Caffeine and Levels of DNA Repair and Oxidative Stress in Women with and without a <b><i>BRCA1</i></b> Mutation

“…Further, in vivo studies involving healthy subjects have shown that daily intake of 3-4 cups of caffeinated coffee was enough to reduce oxidative damage to DNA as measured by the comet assay [35]. Other in vitro and in vivo studies looking at coffee constituents and the antioxidative response have shown similar doses to be sufficient to increase the activity of genes containing antioxidant response elements [16,17]. A recent study which evaluated the transcription factor Nrf2 and coffee in humans reported that regular consumption of 3 cups of coffee/day for 4 weeks significantly increased Nrf2 transcription but varied by Nrf2 genotype [15].…”

“…Studies have shown that oxidative stress may contribute to both the initiation and progression of cancers of several types by contributing to DNA damage and reducing cellular integrity [14]. The cancer-protective effects of coffee and its constituents have been attributed to the ability of coffee to interact with several enzymes and transcription factors in the antioxidant signalling pathways, leading to reduced levels of oxidative stress and improved defence mechanisms [14,15,16,17,18]. These defence mechanisms involve DNA repair, apoptosis signalling and detoxification processes which contribute to a better quality and integrity of DNA [10].…”

“…If so, compounds that minimize oxidative damage (i.e. antioxidants) or enhance repair may impact breast cancer risk [16,17]. Thus, we undertook this study to evaluate whether high levels of caffeine intake were associated with lower levels of oxidative stress and/or improved DNA repair capacity among women with and without a BRCA1 mutation.…”