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

Sangiovanni E, Vrhovsek U, Rossoni G, Colombo E, Brunelli C, Brembati L, Trivulzio S, Gasperotti M, Mattivi F, Bosisio E, Dell'Agli M - PLoS ONE (2013)

Bottom Line: In vivo the protective effect of ellagitannins was evaluated in a rat model of ethanol-induced gastric lesions.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.The effect of ETs on CINC-1 was associated to a decrease of NF-κB nuclear translocation in ETs treated animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, Milano, Italy.

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.

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Effect of ETs from blackberry and raspberry on NF-κB nuclear translocation induced by TNFα and IL-1β.AGS cells at confluence were placed in a medium deprived of FCS, and stimulated with 10 ng/ml TNF-α (panel a) or IL-1β (panel b) for 1 hr. AGS cells were plated at the concentration of 1.5 × 106 cells/ml in 60-mm plates. NF-κB nuclear translocation was assessed using the NF-κB (p65) transcription factor assay kit (Cayman) followed by spectroscopy (signal read 450 nm, 0.1 s). Inhibition by 5 µM parthenolide used as reference inhibitor was 37% on TNF-α induced NF-κB nuclear translocation, and 40% on IL-1β induced nuclear translocation. Results are the mean ± sd of three experiments in triplicate. * p<0.05, ** p<0.01, ***p<0.001.
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pone-0071762-g004: Effect of ETs from blackberry and raspberry on NF-κB nuclear translocation induced by TNFα and IL-1β.AGS cells at confluence were placed in a medium deprived of FCS, and stimulated with 10 ng/ml TNF-α (panel a) or IL-1β (panel b) for 1 hr. AGS cells were plated at the concentration of 1.5 × 106 cells/ml in 60-mm plates. NF-κB nuclear translocation was assessed using the NF-κB (p65) transcription factor assay kit (Cayman) followed by spectroscopy (signal read 450 nm, 0.1 s). Inhibition by 5 µM parthenolide used as reference inhibitor was 37% on TNF-α induced NF-κB nuclear translocation, and 40% on IL-1β induced nuclear translocation. Results are the mean ± sd of three experiments in triplicate. * p<0.05, ** p<0.01, ***p<0.001.

Mentions: ETblack and ETrasp, at 2 µg/ml, inhibited TNFα-induced translocation by 67% and 57% respectively (Figure 4, panel a). The inhibitory effect of ETs on IL-1β induced translocation was much lower (37% and 22% at 2 µg/ml of ETblack and ETrasp respectively) (Figure 4, panel b).


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

Sangiovanni E, Vrhovsek U, Rossoni G, Colombo E, Brunelli C, Brembati L, Trivulzio S, Gasperotti M, Mattivi F, Bosisio E, Dell'Agli M - PLoS ONE (2013)

Effect of ETs from blackberry and raspberry on NF-κB nuclear translocation induced by TNFα and IL-1β.AGS cells at confluence were placed in a medium deprived of FCS, and stimulated with 10 ng/ml TNF-α (panel a) or IL-1β (panel b) for 1 hr. AGS cells were plated at the concentration of 1.5 × 106 cells/ml in 60-mm plates. NF-κB nuclear translocation was assessed using the NF-κB (p65) transcription factor assay kit (Cayman) followed by spectroscopy (signal read 450 nm, 0.1 s). Inhibition by 5 µM parthenolide used as reference inhibitor was 37% on TNF-α induced NF-κB nuclear translocation, and 40% on IL-1β induced nuclear translocation. Results are the mean ± sd of three experiments in triplicate. * p<0.05, ** p<0.01, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3733869&req=5

pone-0071762-g004: Effect of ETs from blackberry and raspberry on NF-κB nuclear translocation induced by TNFα and IL-1β.AGS cells at confluence were placed in a medium deprived of FCS, and stimulated with 10 ng/ml TNF-α (panel a) or IL-1β (panel b) for 1 hr. AGS cells were plated at the concentration of 1.5 × 106 cells/ml in 60-mm plates. NF-κB nuclear translocation was assessed using the NF-κB (p65) transcription factor assay kit (Cayman) followed by spectroscopy (signal read 450 nm, 0.1 s). Inhibition by 5 µM parthenolide used as reference inhibitor was 37% on TNF-α induced NF-κB nuclear translocation, and 40% on IL-1β induced nuclear translocation. Results are the mean ± sd of three experiments in triplicate. * p<0.05, ** p<0.01, ***p<0.001.
Mentions: ETblack and ETrasp, at 2 µg/ml, inhibited TNFα-induced translocation by 67% and 57% respectively (Figure 4, panel a). The inhibitory effect of ETs on IL-1β induced translocation was much lower (37% and 22% at 2 µg/ml of ETblack and ETrasp respectively) (Figure 4, panel b).

Bottom Line: In vivo the protective effect of ellagitannins was evaluated in a rat model of ethanol-induced gastric lesions.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.The effect of ETs on CINC-1 was associated to a decrease of NF-κB nuclear translocation in ETs treated animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, Milano, Italy.

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.

Show MeSH
Related in: MedlinePlus