Modulation of N rf2‐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 N rf2‐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 ( NQO 1) were significantly elevated throughout the observation period (1–8 h), whereas transcription of heme oxygenase 1 ( HO ‐1) and N rf2 was significantly decreased. NQO 1 and HO ‑1 transcription remained unchanged in the ileostomy probands, whereas N rf2‐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 q PCR ( HT 29) 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 PBMC s 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 N rf2‐activating properties of the intestinal anthocyanin degradation product PGA .