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Effects of Hecogenin and Its Possible Mechanism of Action on Experimental Models of Gastric Ulcer in Mice

Effects of Hecogenin and Its Possible Mechanism of Action on Experimental Models of Gastric Ulcer in Mice

Gilberto Santos Cerqueira, Gabriela dos Santos e Silva, Emiliano Rios Vasconcelos, Ana Paula Fragoso de Freitas, Brinell Arcanjo Moura, Danielle Silveira Macedo, Augusto Lopes Souto, José Maria Barbosa Filho, etc.

Eur J Pharmacol. 2012 May 15;683(1-3):260-9.

PMID: 22426163

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP467550	Hecogenin		467-55-0	Price

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