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.
Background/Aims: Anthocyanins are plant-derived dietary components that are highly abundant, for example, in bilberries. We have previously demonstrated that anthocyanins exert anti-inflammatory properties in mouse colitis models and ameliorate disease activity in ulcerative colitis patients. Here, we studied the molecular mechanisms through which anthocyanin-containing bilberry extract (BE) exerts anti-inflammatory effects in human monocytic THP-1 cells. Methods: THP-1 cells were pre-incubated with BE 20 min prior to TNF-a or IFN-γ (100 ng/ml each) stimulation. Signalling protein activation was studied by Western blotting, mRNA expression by quantitative PCR and cytokine secretion by ELISA. Results: IFN-γ-induced phosphorylation of STAT1 and STAT3 was significantly reduced by BE co-treatment. Consequently, levels of mRNA expression and/or cytokine secretion of MCP-1, IL-6, TNF-a, ICAM-1, and T-bet were lower with BE co-treatment. In contrast, BE enhanced TNF-a-mediated p65-NF-γB phosphorylation but reduced ERK1/2 phosphorylation. BE co-treatment further increased TNF-a-induced mRNA expression and secretion of NF-γB target genes, such as IL-6, IL-8, and MCP-1, while mRNA levels of ICAM-1 were reduced. Conclusions: BE co-treatment reduced IFN-γ-induced signal protein activation, pro-inflammatory gene expression, and cytokine secretion, whereas it enhanced TNF-a-induced responses. These findings suggest a distinct role for anthocyanins in modulating inflammatory responses that need to be further studied to fully understand anthocyanin-mediated effects.
Background: Obesity blunts the association of cfPWV with BP, at least in youth. We assessed the impact of BMI in the relationship between carotid artery function (CAF) and central BP. Methods: Stiffness index (b), Elastic modulus (Ep), Arterial Compliance (AC) and local PWV (PWVb) were measured at the common carotid arteries by echo-tracking (Aloka prosound alpha 10), and central BP was assessed with the SphygmoCor device. Patients were classified into 3 groups according to BMI (<25 normal weight; !25-<30 overweight; !30 obesity). Linear regression models, Pearson's correlation coefficient and ANCOVA models (age, gender, heart rate and central PP as covariates) were performed. Results: 222 patients (mean age 42.8 AE 14.2 years; 93 (42%) women; mean BMI 26.6 AE 4.4; 139 (62.6%) hypertensives, 104 (74.8%) under treatment). BMI categories: 85 (38.3%) normal weight, 88 (39.6) overweight, 49 (22.1%) obesity. Age, HR ,central PP showed significant positive association with CAF parameters. BMI categories and gender were not significantly associated with CAF parameters, except for overweight with PWVb (p-value 0.02). There was no significant difference in b, Ep, AC and PWVb between BMI groups after adjusting by covariates. Pearson's correlation coefficient between central SBP and CAF parameters was significantly lower if BMI!25 (â: 0.46, 0.19, 0.13; Ep: 0.69, 0.43, 0.3; AC: -0.48, -0.37, -0.31; PWVâ: 0.66, 0.48, 0.36 for normal weight, overweight and obesity, respectively; p-value for overweight<0.001, p-value for obesity<0.05). Conclusions: BMI categories are not closely related to CAF. BMI might blunt the increment of CAF parameters with rising central BP.
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