Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice

详细信息	查看全文 | 推荐本文 |

• 作者：Gilberto Santos Cerqueira^a ; Gabriela dos Santos e Silva^a ; Emiliano Rios Vasconcelos^a ; Ana Paula Fragoso de Freitas^a ; Brinell Arcanjo Moura^a ; Danielle Silveira Macedo^a ; Augusto Lopes Souto^c ; José ; Maria Barbosa Filho^c ; Luzia Kalyne de Almeida Leal^b ; Gerly Anne de Castro Brito^d ; Caden Souccar^e ; Glauce Socorro de Barros Viana^a ; ^{gbviana@live.com}
• 关键词：Antiulcerogenic activity ; Hecogenin ; Steroid saponin ; Agave sisalana ; Gastroprotection mechanism of action
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 May, 2012
• 卷：683
• 期：1-3
• 页码：260-269
• 文件大小：2538 K

摘要

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.