Chronic gastric inflammation developing after Helicobacter pylori (H. pylori) infection is responsible for either dyspeptic symptom relevant to gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants, especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as well as the eradication regimen. Among several mediators engaged in propagating gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be the principal one, and several prescriptions have been made for decreasing the COX-2 levels. Multiple line of evidence are available for anti-inflammatory action of PPIs beyond acid suppression, but revaprazan, a novel acid pump antagonist launched in clinic, has also been suggested to exert significant anti-inflammatory actions as much as PPI. In the current study, we hypothesized that revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti-inflammatory pharmacological actions. The changes of gastric COX-2 expression as well as responsible transcription factors were measured after H. pylori infection in the presence or absence of revaprazan. Infection of AGS cells with H. pylori induced significant up-regulation of COX-2 in time- and concentration-dependent manners, which was mediated by Akt phosphorylation. Revaprazan treatment significantly inhibited IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Additional rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted. In conclusion, revaprazan imposed significant anti-inflammatory actions on H. pylori infection beyond acid suppression.
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.
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