Attenuation of cysteamine-induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5-lipoxygenase and activating ?-glutamylcysteine synthetase

作者：Choi Ki Seok; Kim Eun Hee; Hong Hua; Ock Chan Young; Lee Jeong Sang; Kim Joo Hyun; Hahm Ki Baik^*

来源：Journal of Gastroenterology and Hepatology, 2012, 27: 13-22.

DOI：10.1111/j.1440-1746.2012.07065.x

• Cochinchina momordica seed extract
• cPLA2
• cysteamine
• duodenal ulcer
• glutathione

Background and Aim: Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H2O2 reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms. Methods: Cochinchina momordica seed extract (50, 100, 200 mg/ kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/ oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1b, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed. Results: Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA2, COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of g-glutamylcysteine synthetase (g-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA2. Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of g-GCS. Conclusion: Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.

• 出版日期2012-4