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

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.

Intestinal Mucosal Barrier Function Restoration in Mice by Maize Diet Containing Enriched Flavan-4-Ols

“…Among all the measurements, F+ (25) tended to have overall a better performance than F+ (15), indicating that this beneficial effect is dose-dependent. This lines up with the findings of similar studies [12,33]. The less notable differences between F+(15) and F+ (25) are likely due to the low-grade inflammation induced by CMC, further studies using acute DSS colitis model should be conducted to clarify this.…”

“…Flavonoid compounds are a large subfamily of phenolic compounds abundant in many of the fruits and vegetables that are essential constituents of our daily diet. Substantial evidence has demonstrated the properties of isolated flavonoids or flavonoid-rich fractions as potent anti-inflammatory agents as well as their protective effects against chronic diseases including IBD [9][10][11][12]. Maize (Zea mays L.) is one of the most important cereal crops all over the globe, colored maize cultivars rich in flavonoid and carotenoid compounds are thought to confer better health benefit than conventional maize.…”

Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model

“…In human monocytic THP-1 cells, bilberry extract reduced interferon-γ (IFN-γ)-induced signal protein activation, pro-inflammatory gene expression and cytokine secretion, and enhanced tumor necrosis factor-α (TNF-α)-induced responses [28] . Even a recent study on biopsy samples of patients with ulcerative colitis treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial revealed reduced amounts of the proinflammatory cytokines IFN-γ and TNF-α [29] .…”

Anthocyane, Heidelbeeren und Curcuma: Wirksame Therapeutika bei Darmentzündungen?

“…Zudem fand sich im Serum dieser Patienten eine Abnahme der entzün-dungsfördernden Zytokine TNF und MCP-1. Diese Beobachtungen konnten bei Patienten, welche nicht suffizient auf die Behandlung ansprachen, nicht gemacht werden [26]. Bei vielen Patienten fand sich 2 Wochen nach Beendigung der Anthocyan-Einnahme jedoch ein Wiederanstieg des Entzündungsmarkers Calprotectin.…”