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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Myocardial infarction is usually induced in small animals by means of invasive procedures: the aim of this study was to cause heart necrosis lesions by non-invasive means. We injected rabbits with isoproterenol (3 mg/kg, i.p.) and vasopressin (0.3 mg/kg/5 min, i.v.) alone and in combination, and studied their effects on myocardial histology, electrocardiographic profiles, the appearance of the plasma cardiac necrosis marker c-troponin I (c-TPN I), hemodynamic parameters (blood pressure, heart rate), the coagulative process partial throboplastine time (PTT), and plasma nitric oxide (NO) levels. In the rabbits treated with vasopressin alone, the ischemic damage was associated with a decrease in NO values, and the appearance of electrocardiographic T-wave inversion and low plasma c-TPN I levels, whereas the animals treated with isoproterenol alone had necrotic bands in the myocardium, plasma c-TPN I, and electrocardiographic modifications (ST-segment changes and T-wave inversion). Combined treatment increased myocardial alterations such as contraction band necrosis, induced the appearance of specific hypoxic lesions such as areas of coagulative necrosis and leukocyte infiltration, and led to higher plasma c-TPN I levels and altered ECG profiles. Both drugs favored a decrease in plasma NO values and further alterations in hemodynamic parameters, such as higher blood pressure and greater procoagulant activity. The myocardial necrosis and modified cardiovascular parameters were attributed to calcium activated processes and the decrease in NO levels. As this model of myocardial damage involves the use of drugs that facilitate the opening of L-calcium channels, we also investigated their effects on cardiovascular parameters and heart histology after pretreatment with the calcium antagonist verapamil; this drug protected against the appearance of histological myocardial lesions, electrocardiographic alterations and high plasma c-TPN I levels, and prevented the hemodynamic and procoagulation changes, but did not affect the decrease in plasma NO values. The protective effects were attributed to the drug's calcium antagonist activity. In conclusion, the injection of isoproterenol and vasopressin induces a myocardial infarction non-invasively and seems to be suitable for studying early myocardial ischemic lesions and the effects of drugs interfering with myocardial damage and its related phenomena.