Beyond acid suppression: mechanisms underlying the beneficial effects of STW 5 in experimental reflux esophagitis (RE)

Proton pump inhibitor (PPI) therapy is the most effective medical treatment for symptom relief in gastro-esophageal reflux disease (GERD). However, up to 40% of patients do not achieve adequate symptom control. STW5 was shown to relieve heartburn and concomitant reflux symptoms in patients with functional dyspepsia and to prevent inflammation in an acute model of RE, without affecting the pH of the refluxate. In the present study, the efficacy of STW5 was assessed in a sub-chronic model of RE, and the underlying mechanisms were investigated. After pre-treatement for 7d with STW5 or omeprazole, esophagitis was induced surgically. Rats were treated for further 10d with the drugs before sacrifice. The esophagi were excised and evaluated macroscopically. Tissue homogenates were used for a proteome-profiler cytokine array. Tissue samples and peripheral blood were analyzed using Agilent whole genome microarray. Both treatments improved macroscopic parameters to similar extents. However, STW5 had a much more pronounced anti-inflammatory effect as evidenced by the cytokine array, which showed a marked increase in the number and amount of cytokines released in the esophagitis group. STW5 inhibited the vast majority of these changes dose dependently. The effect was much more prominent than that of omeprazole, suggesting a direct anti-inflammatory/mucosa protecting action. This was confirmed by microarray analysis. Since gastric acid does not seem to be the only causative agent involved in the pathogenesis of GERD, the present findings suggest that multi-target anti-inflammatory drugs like STW5 might present an alternative/additional treatment option for GERD patients not responding adequately to PPIs.