Back to Search
Start Over
Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2012 May 15; Vol. 683 (1-3), pp. 260-9. Date of Electronic Publication: 2012 Mar 08. - Publication Year :
- 2012
-
Abstract
- This study investigates the gastroprotective effects of hecogenin, a steroid saponin isolated from Agave sisalana, on experimental models of gastric ulcer. Male Swiss mice were used in the models of ethanol- and indometacin-induced gastric ulcer. To clarify the hecogenin mechanism of action, the roles of nitric oxide (NO), sulfhydryls (GSH), K⁺(ATP) channels and prostaglandins were also investigated, and measurements of lipid peroxidation (TBARS assay) and nitrite levels in the stomach of hecogenin-treated and untreated animals were performed. Furthermore, the effects of hecogenin on myeloperoxidase (MPO) release from human neutrophils were assessed in vitro. Our results showed that hecogenin (3.1, 7.5, 15, 30, 60 and 90 mg/kg, p.o.) acutely administered, before ethanol or indomethacin, exhibited a potent gastroprotective effect. Although the pretreatments with L-NAME, an iNOS inhibitor, and capsazepine, a TRPV1 receptor agonist, were not able to reverse the hecogenin effect, this was reversed by glibenclamide, a K⁺(ATP) blocker, and indomethacin in the model of ethanol-induced gastric lesions. The hecogenin pretreatment normalized GSH levels and significantly reduced lipid peroxidation and nitrite levels in the stomach, as evaluated by the ethanol-induced gastric lesion model. The drug alone increased COX-2 expression and this effect was further enhanced in the presence of ethanol. It also decreased MPO release and significantly protected the gastric mucosa. In conclusion, we showed that hecogenin presents a significant gastroprotective effect that seems to be mediated by K⁺(ATP) channels opening and the COX-2/PG pathway. In addition, its antioxidant and anti-inflammatory properties may play a role in the gastroprotective drug effect.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Anti-Ulcer Agents administration & dosage
Anti-Ulcer Agents pharmacology
Antioxidants administration & dosage
Antioxidants pharmacology
Antioxidants therapeutic use
Cyclooxygenase 2 metabolism
Dose-Response Relationship, Drug
Ethanol
Gastric Mucosa metabolism
Glutathione metabolism
Humans
Indomethacin
KATP Channels metabolism
Lipid Peroxidation drug effects
Male
Mice
Neutrophil Activation drug effects
Nitric Oxide metabolism
Prostaglandins metabolism
Random Allocation
Sapogenins administration & dosage
Sapogenins pharmacology
Stomach immunology
Stomach Ulcer immunology
Stomach Ulcer metabolism
Anti-Ulcer Agents therapeutic use
Disease Models, Animal
Sapogenins therapeutic use
Stomach drug effects
Stomach Ulcer drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 683
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22426163
- Full Text :
- https://doi.org/10.1016/j.ejphar.2012.02.043