Abstract

Purpose: The present study was designed to evaluate the anti-inflammatory, anti-oxidative stress activities, and differential regulation of Nrf2-mediated genes by Rhei rhizoma and Glycyrrhiza uralensis mixture extracts (RGE) and to determine the usefulness of antioxidants in the treatment of reflux esophagitis. Methods: Reflux esophagitis was induced by ligation with a 2-0 silk thread both the pylorus and the transitional junction between the forestomach and the corpus, in Sprague-Dawley rats. Results: Our results show that RGE administration markedly ameliorated mucosal damage upon histological evaluation. In serum, RGE significantly suppressed the oxidative stress biomarkers, such as reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substances (TBARS). The rats with reflux-induced esophagitis exhibited down-regulation of antioxidant-related proteins such as nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels in the esophagus; however, the levels with treatment of RGE were significantly higher than those in vehicle-administrated and reflux-induced esophagitis rats. RGE treatment caused significant reductions in activation of NFB transcription factor, especially the p65 subunit, in accordance with the significantly higher levels of inhibitory protein of NFB expression. Thus, RGE significantly exhibited potent antiinflammatory activities by suppressing the protein expression levels of proinflammatory proteins, COX-2 and iNOS, in the esophagus tissue. Conclusion: Reflux esophagitis caused considerable levels of oxidative stress in the esophageal mucosa and the administration of RGE reduced the esophageal mucosa damage through the regulation of a potential cross-talks between Nrf2 and NFB pathways. Our findings should be considered as supplementary therapy in the prevention or treatment of reflux esophagitis. Contact: Joo Young Lee, jyhappy0130@hanmail.net

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