EFFECT OF BLUEBERRY (Vaccinium spp.) POLYPHENOLS OBTAINED USING A NATURAL DEEP EUTECTIC SOLVENT (NADES) IN A RAT MODEL OF GASTRIC ULCER: REMARKABLE ROLE FOR ANTHOCYANINS

This study aimed to investigate the gastroprotective effect of biocompatible crude blueberry extract (CE) obtained using natural deep eutectic solvent (NADES) and its fractions anthocyanin-rich fraction (ARF) and non-anthocyanin phenolic fraction (NAPF) in a model of ethanol-induced (EtOH) gastric ulcer in rats. Wistar rats were treated daily (via gavage) for 14 days with water, NADES vehicle, CE (10.0 mg of total polyphenols kg-1 of body weight - b.w.), ARF (4.2 mg kg-1 b.w.), NAPF (5.8 mg kg-1 b.w.) or lansoprazole (LAN) (30.0 mg kg-1 b.w), a standard drug for gastric ulcer treatment. ARF and NAPF were administered at doses equivalent to their occurrence in CE. After a 12-hour fasting, animals received 75% ethanol (2 mL kg-1) to induce gastric ulcer. The administration of EtOH caused histological gastric damage evidenced by disseminated hemorrhage, neutrophil infiltration and loss of glandular structure. Only pretreatment with CE completely preserved the integrity of gastric mucosa. GSH/GSSG ratio was decreased by 44% in the water-EtOH group compared to the control group. The pretreatments with CE, ARF and LAN were able to prevent this alteration (about 85, 81 and 99%, respectively). Gastric ulcer increased by 2.6-fold the serum activity of myeloperoxidase compared to the control group and pretreatments with CE, ARF or LAN completely prevented this increase. The fecal concentrations of short chain fatty acids (SCFA) and fecal pH were unaffected by administration of ethanol when compared to the control group, but the pretreatment with ARF increased by 1.5-fold the fecal content of acetic acid and reduce about 5% the fecal pH. Our results demonstrate that NADES crude extract of blueberry exhibits a gastroprotective effect. The anthocyanin fraction appears to be responsible for preventing GSH depletion and had greater anti-inflammatory effect than the non-anthocyanin fraction, besides exerting a prebiotic effect indicated by the increase in SCFA.