RESUMO
The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE(2) production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes.
Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Indigofera/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Cicatrização/efeitos dos fármacos , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Modelos Animais de Doenças , Etanol/efeitos adversos , Suco Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Masculino , Metaboloma , Metabolômica , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Prostaglandinas/biossíntese , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Metabolismo Secundário , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismo , Compostos de Sulfidrila/farmacologia , Superóxido Dismutase/metabolismoRESUMO
The bark of Croton cajucara Benth. is used in Brazilian folk medicine to treat gastrointestinal disorders. Transdehydrocrotonin (DHC) isolated from the bark of Croton cajucara has antiulcerogenic activity25. The presence of similar activity in semi-synthetic crotonin obtained from dehydrocrotonin from Croton cajucara was observed in gastric ulcer-induced models (HCl/ethanol, ethanol, indomethacin, stress and pylorus ligature). The aim of the present study was to assess the mechanisms involved in the antiulcerogenic activity of semi-synthetic crotonin. We investigated the effects of semi-synthetic crotonin on the response to histamine of right atria isolated from guinea pigs and on the response to carbachol of stomach fundus strips from rats. Semi-synthetic crotonin (3, 10 or 30 mM) induced a shift to the right in the concentrationresponse curves to carbachol in the isolated rat stomach at the pD2 level (pD2: 5.42±0.05, 5.76±0.061, 5.77±0.076, 6.48±0.012, respectively), without any alteration in the maximum response. Semi-synthetic crotonin also induced a shift to the right in the concentration-response curves to histamine in guinea pig right atria, pD2 (5.54±0.06, 6.01±0.06, 5.89±0.06, 5.92±0.03) and ( percent) maximum response (80±6.18, 118±6.18, 114±6.18, 122±1.4), respectively. Thus, the protective effect of semi-synthetic crotonin on induced gastric lesions could be due to antagonism of histaminergic and cholinergic effects on gastric secretion.