Mecanismos envolvidos na atividade gastroprotetora do extrato hexânico das folhas de Celtis iguanaea (JACQ.) Sargent (Cannabaceae) e da fração aquosa do extrato hidroacetônico de Eugenia uniflora L. (Myrtaceae)

Abstract

Peptic ulcer disease is a major cause of morbidity and mortality, and is characterized by deep lesions in the gastric mucosa. The pathophysiological of peptic ulcer is described as an imbalance between aggressive factors such as hydrochloric acid, pepsin and protective factors of gastric mucosa, such as mucus, bicarbonate, nitric oxide (NO), prostaglandins and blood flow. In Brazil, ethnopharmacological studies report the use of Celtis iguanaea (Jacq.) Sargent and Eugenia uniflora L. for the treatment of gastrointestinal disorders. The objective of this study was to investigate the possible mechanisms involved in the gastroprotective activity of extract hexane of leaves Celtis iguanaea (Jacq.) Sargent (EHEG), of the aqueous fraction of hydroacetonic extract from the leaves of Eugenia uniflora (FAHP) and phytoconstituentisolated from FAHP (Oenothein B). Male albino Swiss mice adult weighing between 35-40 g or male albino Wistar rats adult weighing between 180-200 g. Were used in this study the EHEG produced antiulcer activity in different in vivo models, such as stress, HCl/EtOH and acetic acid induced ulcer. The EHEG at dose of 100 mg/kg administered orally (p.o.) or intraduodenally (i.d.) increased the binding capacity of the Alcian blue adhered to the gastric mucus. In model to evaluate the role of α2-adrenoceptor was observed that pretreatment with yohimbine (an antagonist α2-adrenergic) reduced gastroprotection produced by EHEG (100 mg/kg, p.o.). In model to assess the role of NO was observed that pretreatment with L-NAME (NG-L-Nitroarginine methyl ester - non-specific NOS inhibitor) reduced gastroprotection exercised by EHEG (100 mg/kg, p.o.) and in model to evaluate the role of prostaglandins (PGs) endogenous, was observed that pretreatment with indomethacin (an inhibitor of cyclooxygenase enzyme) reduced the astroprotection effect of EHEG (100 mg/kg, p.o.). This study also showed that animals treated with FAHP in doses of 10, 30, 100, 300 and 1000 mg/kg or vehicle (distilled water) prduced not activity, when compared with the control group in overral pharmacological activity test. FAHP has antiulcer activity in different models of induced ulcers in vivo, such as indomethacin, stress and HCl/EtOH. FAHP in the dose of 300 mg/kg given orally increased binding capacity Alcian blue adhered to the gastric mucosa and the levels of GSH. In assessing the antissecretory activity, FAHP (300 mg/kg, i.d.) was able to reduce the free acidity (pH) and total acidity. In model to evaluate the role of NO was observed that retreatment with L-NAME did not reduce the gastroprotection exerted by FAHP. The oenoteína B also showed antiulcerogenic activity in different models of induced ulcers in ivo, such as indomethacin, HCl/EtOH and pyloric ligation. In an attempt to elucidate the possible mechanisms of action were performed ex vivo bioassays. The oenothein B (15 mg/kg,p.o.) was able to increase the activity of catalase (CAT) in the gastric mucosa. In model to evaluate the role of prostaglandins (PGs) Endogenous was observed that retreatment with indomethacin, reduced gastroprotection produced by oenothein B. However, the treatment with oenothein B did not prevented the reduction of the levels of PGE2 in the gastric mucusof rats pretreated with indomethacin. In the study of antissecretory activity, treatment with oenothein B (15 mg/kg i.d.) was able to reduce the amount of gastric acid secretion (mL) and total acidity. The findings of this study suggest that EHEG, FAHP and oenothein B have gastroprotective activity against the several ulcerogenic agents used. The gastroprotection was related mainly to the increase of protective factors (NO, PGs, mucus or antioxidant activity), but also there was a reduction of aggressive factors (gastric acid secretion).