Modulation of Nrf2-dependent gene transcription by bilberry anthocyanins in vivo.
In a human pilot intervention study (healthy + ileostomy probands), the questions were addressed whether in vivo consumption of an anthocyanin-rich bilberry (Vaccinium myrtillius L.) pomace extract (BE) affects (i) the transcription of Nrf2-dependent genes in peripheral blood mononuclear cells (PBMC), indicative for systemic effects, and (ii) the level of oxidative DNA damage in these cells. In healthy test subjects transcripts of NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly elevated throughout the observation period (1-8 h), whereas transcription of heme oxygenase 1 (HO-1) and Nrf2 was significantly decreased. NQO1 and HO-1 transcription remained unchanged in the ileostomy probands, whereas Nrf2-transcription was suppressed in both groups. Decrease in oxidative DNA damage was observed 2 h after BE consumption again only in healthy subjects. In vitro studies using a reporter gene approach (CHO) and qPCR (HT29) indicate that not the intact anthocyanins/anthocyanidins are the activating constituents but the intestinal degradation product phloroglucinol aldehyde (PGA). Taken together, consumption of anthocyanin-rich BE was found to modulate Nrf2-dependent gene expression in PBMCs indicative for systemic activity. Limitation of the effect to healthy test subjects suggests a role of colonic processes for bioactivity, supported by the results on Nrf2-activating properties of the intestinal anthocyanin degradation product PGA.
Department of Food Chemistry and Toxicology, University of Vienna, Vienna, Austria.
Christopher
C
Kropat
Dolores
D
Mueller
Ute
U
Boettler
Kristin
K
Zimmermann
Elke H
EH
Heiss
Verena M
VM
Dirsch
Dorothee
D
Rogoll
Ralph
R
Melcher
Elke
E
Richling
Doris
D
Marko
D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000097:blood; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D007081:Ileostomy; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010865:Pilot Projects; D010936:Plant Extracts; D020011:Protective Agents / Q000494:pharmacology; D014158:Transcription, Genetic; D029800:Vaccinium myrtillus / Q000737:chemistry*
D000872:Anthocyanins; D001547:Benzaldehydes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D020011:Protective Agents; C073305:Vaccinium myrtillus extract; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005978:Glutathione; C535196:2,4,6-trihydroxybenzaldehyde