Bilberry-Derived Anthocyanins Modulate Cytokine Expression in the Intestine of Patients with Ulcerative Colitis.

Sofia Roth,Michael Scharl,Silvia Lang,Luc Biedermann,Claudia Gottier,Gerhard Rogler,Marianne R Spalinger,Jonas Zeitz,Achim Weber,Giorgos Bamias

doi:10.1371/journal.pone.0154817

Abstract

Background/AimsWe previously demonstrated that anthocyanin-rich bilberry extract (ARBE) inhibits IFN-γ-induced signalling and downstream effects in human monocytic cells and ameliorates disease activity in ulcerative colitis (UC) patients. Here, we studied the molecular mechanisms of ARBE-mediated effects in vitro and by analysing colonic tissue and serum samples of UC patients treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial.MethodsColon specimens obtained during an open pilot study using ARBE for the treatment of mild-to-moderate UC were analyzed by immunohistochemistry. Cytokine levels in patients’ serum were quantified by ELISA. Cell culture experiments were performed using THP-1 monocytic cells.ResultsARBE treatment inhibited the expression of IFN-γ-receptor 2 in human THP-1 monocytic cells. Colon biopsies of UC patients who responded to the 6-week long ARBE treatment revealed reduced amounts of the pro-inflammatory cytokines IFN-γ and TNF-α. Levels of phosphorylated (activated) p65-NF-κB were reduced in these patients. Further, patients with successful ARBE treatment featured enhanced levels of Th17-cell specific cytokine IL-22 and immunoregulatory cytokine IL-10 as well as reduced serum levels of TNF-α and MCP-1, but enhanced levels of IL-17A, in contrast to patients that did not reach remission after ARBE treatment.ConclusionsOur data suggest a molecular mechanism underlying the anti-inflammatory effects of ARBE treatment in UC patients by modulating T-cell cytokine signalling and inhibiting IFN-γ signal transduction. These data are of particular interest, since ARBE is a promising therapeutic approach for the treatment of IBD.

Highlights

Phenols are plant-derived molecules with anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-adipogenic and neuroprotective properties [1,2]
We previously demonstrated that anthocyanin-rich bilberry extract (ARBE) inhibits IFN-γinduced signalling and downstream effects in human monocytic cells and ameliorates disease activity in ulcerative colitis (UC) patients
Colon biopsies of UC patients who responded to the 6-week long ARBE treatment revealed reduced amounts of the pro-inflammatory cytokines IFN-γ and TNF-α

Summary

Introduction

Phenols are plant-derived molecules with anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-adipogenic and neuroprotective properties [1,2] They consist of one or more (polyphenols) aromatic ring(s) with at least one hydroxyl group attached. Anthocyanidins form a crucial sub-class of dietary flavonoids and are widespread in fruits and flowers where they account for the blue, purple and red colours In these plant-derived forms they are commonly conjugated to sugars or organic acids and named anthocyanins [1,2]. Berries, red wines, leafy and root vegetables and certain whole grain cereals comprise relative high amounts of anthocyanins Due to their health-promoting and protective characteristics substantial interest in phenols has emerged lately [3]. Additional mechanisms such as direct interference with receptor-regulated signalling pathways and gene expression have been postulated [7,8,9]

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