Ellagitannins from Rubus berries for the control of gastric inflammation: in vitro and in vivo studies

PLoS One. 2013 Aug 5;8(8):e71762. doi: 10.1371/journal.pone.0071762. Print 2013.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Drug Evaluation, Preclinical
  • Fruit* / chemistry
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Gastritis / pathology
  • Gastritis / prevention & control*
  • Humans
  • Hydrolyzable Tannins / isolation & purification
  • Hydrolyzable Tannins / pharmacology*
  • Male
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar
  • Rosaceae* / chemistry
  • Tumor Cells, Cultured

Substances

  • Anti-Inflammatory Agents
  • Hydrolyzable Tannins
  • Plant Extracts
  • ellagitannin

Grant support

The present research was partially funded by “Research Center for Characterization and Safe Use of Natural Compounds-G. Galli”. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.