Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis

To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. METHODSA surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations. RESULTSThe CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations. CONCLUSIONIn the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.