Abstract
Ellagitannins have shown anti-inflammatory and anti-Helicobacter pylori properties; however, their anti-inflammatory activity at gastric level was not previously investigated. The aim of this research was to evaluate the effects of ellagitannins from Rubus berries on gastric inflammation. Ellagitannin enriched extracts (ETs) were prepared from Rubus fruticosus L. (blackberry) and Rubus idaeus L. (raspberry). The anti-inflammatory activity was tested on gastric cell line AGS stimulated by TNF-α and IL-1β for evaluating the effect on NF-kB driven transcription, nuclear translocation and IL-8 secretion. In vivo the protective effect of ellagitannins was evaluated in a rat model of ethanol-induced gastric lesions. Rats were treated orally for ten days with 20 mg/kg/day of ETs, and ethanol was given one hour before the sacrifice. Gastric mucosa was isolated and used for the determination of IL-8 release, NF-kB nuclear translocation, Trolox equivalents, superoxide dismutase and catalase activities. In vitro, ETs inhibited TNF-α induced NF-kB driven transcription (IC50: 0.67–1.73 µg/mL) and reduced TNF-α-induced NF-kB nuclear translocation (57%–67% at 2 µg/mL). ETs inhibited IL-8 secretion induced by TNF-α and IL-1β at low concentrations (IC50 range of 0.7–4 µg/mL). Sanguiin H-6 and lambertianin C, the major ETs present in the extracts, were found to be responsible, at least in part, for the effect of the mixtures. ETs of blackberry and raspberry decreased Ulcer Index by 88% and 75% respectively and protected from the ethanol induced oxidative stress in rats. CINC-1 (the rat homologue of IL-8) secretion in the gastric mucosa was reduced in the animals receiving blackberry and raspberry ETs. The effect of ETs on CINC-1 was associated to a decrease of NF-κB nuclear translocation in ETs treated animals. The results of the present study report for the first time the preventing effect of ETs in gastric inflammation and support for their use in dietary regimens against peptic ulcer.
Highlights
The gastrointestinal tract represents an important barrier between the human hosts and microbial populations
ETs from blackberry (ETblack) and ETs from raspberry (ETrasp) inhibited the increase of NF-kB driven transcription induced by TNFa in a concentration dependent manner
Polyphenols are a class of heterogeneous compounds that are recognized to possess several biological activities
Summary
The gastrointestinal tract represents an important barrier between the human hosts and microbial populations. One potential consequence of host-microbial interactions is the development of mucosal inflammation, which can lead to gastritis and ulcer. Helicobacter pylori (H. pylori), a Gram-negative pathogen that colonizes the stomach of humans and primates, is the most responsible for these inflammatory processes. H. pylori infection in humans represents a serious public health concern: the WHO classifies this bacterium as a Type 1 carcinogen. The clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors. The pattern and distribution of gastritis strongly correlate with the risk of clinical duodenal or gastric ulcers, mucosal atrophy, gastric carcinoma, or gastric lymphoma
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