Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria. Coyoacán 04510, México.
Fundam Clin Pharmacol. 2011 Dec;25(6):717-22. doi: 10.1111/j.1472-8206.2010.00897.x. Epub 2010 Nov 24.
Carbenoxolone, a semi-synthetic triterpenoid, exhibits gastroprotective activity related to the participation of nitric oxide (NO); however, the complete NO/(c) GMP/K(ATP) channels pathway for carbenoxolone is unknown. Therefore the aim of this study was to examine the NO/(c) GMP/K(ATP) channels pathway as the gastroprotective mechanism of carbenoxolone in the ethanol-induced gastric injury model in the rat. Oral administration of carbenoxolone (30 mg/kg, p.o.) exhibited gastroprotective effect against ethanol-induced gastric injury in rats. Pretreatment with N(G) -nitro-l-arginine methyl ester (L-NAME, 70 mg/kg, i.p.); 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, guanylate cyclase inhibitor, 10 mg/kg, i.p.); or glibenclamide (K(ATP) channels inhibitor, 1 mg/kg, i.p.) reversed the gastroprotective effect of carbenoxolone for ethanol-induced gastric injury. Furthermore, gastric prostaglandins and NO levels increased after carbenoxolone administration in ethanol-induced gastric injury in rats. In conclusion, our results suggest that the increase of NO levels in gastric tissue after pretreatment with carbenoxolone activates the NO/(c)GMP/K(ATP) channels pathway, the principal gastroprotective mechanism of carbenoxolone.
甘草次酸，一种半合成三萜，具有与一氧化氮（NO）参与相关的胃保护活性；然而，甘草次酸的完整 NO/(c)GMP/K(ATP) 通道途径尚不清楚。因此，本研究旨在研究 NO/(c)GMP/K(ATP) 通道途径作为甘草次酸在乙醇诱导的大鼠胃损伤模型中的胃保护机制。口服甘草次酸（30mg/kg，po）对乙醇诱导的大鼠胃损伤表现出胃保护作用。预先给予 N(G)-硝基-l-精氨酸甲酯（L-NAME，70mg/kg，ip）；1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮（ODQ，鸟苷酸环化酶抑制剂，10mg/kg，ip）；或格列本脲（K(ATP) 通道抑制剂，1mg/kg，ip）逆转了甘草次酸对乙醇诱导的大鼠胃损伤的胃保护作用。此外，在乙醇诱导的大鼠胃损伤中，甘草次酸给药后胃组织中前列腺素和 NO 水平增加。总之，我们的结果表明，甘草次酸预处理后胃组织中 NO 水平的增加激活了 NO/(c)GMP/K(ATP) 通道途径，这是甘草次酸的主要胃保护机制。
J Ethnopharmacol. 2011-6-22
J Pharm Pharmacol. 2005-8
Int J Mol Sci. 2017-4-17
Zotero 插件