RESUMEN
Thymol, a monoterpene phenol derivative of cymene, is found in abundance in the essential oils of Thymus, Origanum, and Lippia species. The present study investigated the gastroprotective actions of thymol (10, 30, and 100 mg/kg, p.o.) in the acute (ethanol- and nonsteroidal anti-inflammatory drug-induced ulcers) and chronic (acetic acid-induced ulcers) ulcer models in rats. Some of the mechanisms underlying to the gastroprotective effect of thymol were investigated in the ethanol-induced ulcer model. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligature model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of thymol was performed using the agar-well diffusion method. Thymol (10, 30, and 100 mg/kg) produced dose dependent reduction (P < 0.01) on the total lesion area in the ethanol-induced ulcer model. The gastroprotective response caused by thymol (30 mg/kg) was significantly attenuated (P < 0.001) by intraperitoneal treatment of rats with indomethacin (a non-selective inhibitor of cyclo-oxygenase, 10 mg/kg) and glibenclamide (ATP-sensitive K(+) channel blocker, 10 mg/kg), but not by DL-Propargylglycine (PAG, a cystathionine-γ-lyase inhibitor, 25 mg/kg) and Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME, a non-selective inhibitor of nitric oxide synthase, 70 mg/kg). Thymol (30 and 100 mg/kg) also reduced the ulcer index (P < 0.05) and the total lesion area (P < 0.001) in the indomethacin- and acetic-acid-induced ulcer models, respectively. In the model pylorus ligature, the treatment with thymol failed to significantly change the gastric secretion parameters. However, after treatment with thymol (30 and 100 mg/kg), there was a significant increase (P < 0.01) in mucus production. Thymol no showed anti-H. pylori activity in vitro. Collectively, the present results provide convincing evidence that thymol displays gastroprotective actions on the acute and chronic ulcer models through mechanisms that involve increased in the amount of mucus, prostaglandins, and ATP-sensitive K(+) channels.
Asunto(s)
Mucinas Gástricas/metabolismo , Canales KATP/metabolismo , Moco/metabolismo , Prostaglandinas/metabolismo , Sustancias Protectoras/farmacología , Úlcera Gástrica/prevención & control , Timol/farmacología , Ácido Acético , Enfermedad Aguda , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol , Femenino , Helicobacter pylori/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Microbiana , Sustancias Protectoras/administración & dosificación , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Relación Estructura-Actividad , Timol/administración & dosificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia pyramidalis Tul. (Fabaceae), known as "catingueira", is an endemic tree of the Northeast region of Brazil. This plant, mainly inner bark and flowers, has been used in traditional medicine to treat gastritis, heartburn, indigestion, stomachache, dysenteries, and diarrheas. MATERIALS AND METHODS: The ethanol extract of C. pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300 mg/kg, in the ethanol-induced ulcer model and some of the mechanisms underlying to the gastroprotective effect of this plant investigated. RESULTS: The ethanol extract of C. pyramidalis inner bark (100 mg/kg) produced reduction (P < 0.001) on the total lesion area in the ethanol-induced gastric damage. The gastroprotective response caused by the ethanol extract (100 mg/kg) was significantly attenuated (P < 0.05) by intraperitoneal treatment of rats with DL-Propargylglycine (PAG, a cystathionine-γ-lyase inhibitor; 25 mg/kg), but not by Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME, an inhibitor of nitric oxide synthase; 70 mg/kg), and confirmed by microscopic evidence. The ethanol extract significantly decreased the number of mucosal mast cells compared to vehicle-treated group. The inflammatory cells of the ethanol extract (100 mg/kg)-treated ulcerated rats exhibited an upregulation of interleukin (IL)-4 protein expression and downregulation of inducible nitric oxide synthase (iNOS) expression, observed by immunohistochemistry and flow cytometer. CONCLUSIONS: The present results suggest that the ethanol extract of C. pyramidalis produced dose-related gastroprotective response on ethanol-induce ulcer in rats through mechanisms that involved an interaction with endogenous hydrogen sulfide and reduction of inflammatory process with imbalance between pro-inflammatory and anti-inflammatory mediators, supporting the popular usage of this plant.
Asunto(s)
Antiulcerosos/uso terapéutico , Caesalpinia , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/farmacología , Etanol , Femenino , Mucosa Gástrica/metabolismo , Sulfuro de Hidrógeno/metabolismo , Interleucina-4/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fitoterapia , Corteza de la Planta , Extractos Vegetales/farmacología , Ratas Wistar , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia pyramidalis Tul. (Fabaceae), known as "catingueira", has been used in folk medicine in the treatment of various disorders such as gastritis, heartburn, indigestion, and stomach ache. However, the gastroprotective properties of this species have not yet been studied. MATERIALS AND METHODS: The ethanol extract of Caesalpinia pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300 mg/kg. The antiulcer assays were performed using the ethanol- and nonsteroidal anti-inflammatory drug-induced ulcer models. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligated model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of the ethanol extract of Caesalpinia pyramidalis was performed using the agar-well diffusion and broth microdilution methods. RESULTS: The ethanol extract (30, 100, and 300 mg/kg) produced dose dependent inhibition (P<0.01) on the ulcer lesion index, the total lesion area, and the percentage of lesion area in the ethanol-induced ulcer model. The ethanol extract (30, 100, and 300 mg/kg) also reduced (P<0.001) the ulcer index in the indomethacin-induced ulcer model. In the model ligature pylorus, the treatment with Caesalpinia pyramidalis ethanol extract failed to significantly change the gastric secretion parameters. However, after treatment with the ethanol extract of Caesalpinia pyramidalis (30, 100, and 300 mg/kg), there was a significant increase (P<0.05) in mucus production. The ethanol extract showed anti-Helicobacter pylori activity, with inhibition halos of 12.0 ± 1.7 mm at 10,000 µg/mL. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of the ethanol extract were of 625 and 10,000 µg/mL, respectively. CONCLUSIONS: Collectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis displays gastroprotective actions, supporting the folkloric usage of the plant to treat various gastrointestinal disturbances.