RESUMEN
In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10 mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500 mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01 µg/ml as compared to the IC50 value of omeprazole (30.24 µg/ml) confirming its anti-secretory activity.
Asunto(s)
Antiulcerosos/uso terapéutico , Taninos Hidrolizables/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Estómago/efectos de los fármacos , Terminalia/química , Animales , Antiulcerosos/farmacología , Aspirina , Modelos Animales de Enfermedad , Etanol , Femenino , Frutas , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Concentración de Iones de Hidrógeno , Taninos Hidrolizables/farmacología , Concentración 50 Inhibidora , Ligadura , Masculino , Mucinas/metabolismo , Omeprazol/farmacología , Omeprazol/uso terapéutico , Extractos Vegetales/farmacología , Inhibidores de la Bomba de Protones , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/etiología , Úlcera Gástrica/metabolismo , Sucralfato/farmacología , Sucralfato/uso terapéuticoRESUMEN
Our interest in development of hyaluronidase inhibitors as male antifertility agents led to identification of Terminalia chebula (T. chebula) plant with hyaluronidase (HAase) inhibitory activity of human spermatozoa ( approximately 93% inhibition) and rat caudal epididymal spermatozoa ( approximately 86% inhibition) in vitro at 30 mg/ml. We further demonstrated inhibition of hyaluronidase activity of testis and epididymal spermatozoa in vivo coincident with antispermatogenic activity and contraceptive efficacy of TC extract administered at 50 and 100mg/kg/day orally for 60 days in male albino rats. The significant decrease in motility, count and increase in morphological abnormalities of epididymal spermatozoa and severe reduction in fertility (-100%) of male rats treated with T. chebula fruit extract at 100mg/kg dose could be attributed to either direct effect on testis or direct or indirect interference with sperm maturation in epididymis, and/or inhibition of testicular and epididymal sperm hyaluronidase enzyme in vivo probably caused by flavonoids like tannins present in T. chebula.