Modulation of Inflammatory Gene Expression by a Bilberry (Vaccinium myrtillus L.) Extract and Single Anthocyanins Considering Their Limited Stability under Cell Culture Conditions

Abstract

Studies with nonintestinal models indicate that anthocyanin-rich extracts can modulate inflammatory gene expression and may help prevent development of inflammatory bowel diseases (IBD). This work investigated the influence of a bilberry ( Vaccinium myrtillus L.) extract (BE) and comprising anthocyanins on pro-inflammatory genes in IFN-γ/IL-1β/TNF-α stimulated human colon epithelial cells (T84) by qRT-PCR and cytokine arrays. Moreover, the stability of selected anthocyanins under cell culture conditions was examined to assess their anti-inflammatory properties. BE and single anthocyanins significantly inhibited the expression and secretion of IBD-associated pro-inflammatory mediators (TNF-α, IP-10, I-TAC, sICAM-1, GRO-α) in the stimulated cells. The anti-inflammatory activity thereby strongly depends on the aglycon structure (hydroxylation and methylation pattern) and the sugar moiety. In contrast to anthocyanidins, which were highly unstable in cell culture medium, suggesting that their degradation products might contribute to the inhibitory effects assigned to the parent compounds, anthocyanins have higher stability and may directly contribute to BE's effects.

Bilberry-Derived Anthocyanins Prevent IFN-γ-Induced Pro-Inflammatory Signalling and Cytokine Secretion in Human THP-1 Monocytic Cells

“…We demonstrated that not only STAT1 and STAT3 phosphorylation was inhibited by BE but also target gene expression (IL-6, MCP-1, ICAM-1, and T-bet) and cytokine secretion (MCP-1 and TNF-α). Our data correlate with Triebel et al [10] who evaluated effects of BE in human colon epithelial cells T84. In our experiments, we confirmed that BE prevents IFN-γ-induced pro-inflammatory signalling in THP-1 mononuclear cells and T84 IEC.…”

“…Various studies provide evidence that anthocyanin extracts inhibit inflammatory gene expression in vitro [8,9,10]. Moreover, it has been demonstrated that anthocyanins from bilberries (also called blueberries) decrease pro-inflammatory cytokine serum levels and attenuate the severity of experimental colitis in mice [11,12,13].…”

Anti-inflammatory effects of anthocyanins-rich extract from bilberry (Vaccinium myrtillusL.) on croton oil-induced ear edema andPropionibacterium acnesplus LPS-induced liver damage in mice

“…These pro-inflammatory mediators are regulated by NF-kB during the pathogenesis of inflammation. Previous studies found that both anthocyanins-rich extracts and single anthocyanins can modulate gene expression of pro-inflammatory mediators in vitro and in vivo (Chao et al, 2010;Triebel et al, 2012;Yun et al, 2008). Furthermore, Karlsen et al (2007) discovered strong antiinflammatory effects of anthocyanins by their inhibition of NF-kB and pro-inflammatory chemokine expression in monocytes.…”

Immunomodulatory Effect of a Wild Blueberry Anthocyanin-Rich Extract in Human Caco-2 Intestinal Cells

“…The ACN profile of the WB used in the current research differs from that of previous studies in both qualitative and quantitative composition. 28,29 Generally, Mv-, Dp-, Cy-, Pt-, and Pe-glycosides are the most abundant ACNs found in wild blueberry. 9,30,31 In the ACN-rich fraction prepared for this study that originated from wild blueberry (Vaccinium angustifolium), the dominant compounds were Mvglycosides (35% of the total ACN amount), Dp-glycosides (31%), and Cy-glycosides (19%).…”