Planta Med 2013; 79 - SL7
DOI: 10.1055/s-0033-1351833

A multitarget approach by STW5: the inhibition of a proinflammatory signature, the increase of membrane-bound mucins and the restoration of barrier function improves esophagitis in rats

G Ulrich-Merzenich 1, MT Khayyal 2, O Kelber 3, D Weiser 3, H Abdel-Aziz 4
  • 1Medical clinic III, UKB, University of Bonn, Germany
  • 2Faculty of Pharmacy, Cairo University, Egypt
  • 3Scientific Dpt., Stegerwald Arzneimittelwerk GmbH, Darmstadt, Germany
  • 4Institute of Pharmaceutical Chemistry, University of Münster, Germany Scientific Dpt., Stegerwald Arzneimittelwerk GmbH, Darmstadt, Germany

Gastroesophageal reflux disease (GERD) is one of the most common GI-diagnosis. Proton pump inhibitors (PPIs) constitute the main treatment, but up to 40% of patients do not achieve adequate symptom control. STW5, a multi-component herbal preparation, was shown to relief concomitant reflux symptoms in patients with functional dyspepsia.

Therefore, the efficacy of STW5 was assessed in a subchronic model of GERD. Rats were pre-treated for 7 d with STW5 (0.5 or 2 ml/kg) or Omeprazole (O). Esophagitis was induced surgically and treatment continued for further 10 d before rats were sacrificed and all esophagi were excised. RNA was isolated from defined tissue areas and analyzed by Agilent whole genome microarray.

Vehicle treated controls showed marked esophagitis accompanied by significant upregulation of transcripts of well-known markers of inflammation like IL-1ß (14x), IL-6 (11x), TNF-α (11x), CINC-1,2&3 (IL-8 analoga) and transcripts so far not linked to esophagitis like CXCL1 (CXC-motif ligand 1, melanoma growth factor; 32x) or CCL4 (macrophage inflammatory protein 1; 34x).

Both treatments improved esophagitis. Proteom-profiling of tissue homogenates revealed a stronger and dose-dependent downregulation of proinflammatory mediators like IL-1ß or CXCL1 in the STW5 groups compared to O. This was also reflected in the transcript profile. IL-1ß and especially members of the C- and CXC chemokine families (CCL4, CXCL1, 2, 3, 6 & 10) were strongly downregulated (10 to 33x). IL-6 and TNF-a were down regulated by STW5 in the range of their upregulation. In addition, the transmembrane mucin MUC16 and members of the claudin family (Claudin 3, 23), crucial in the formation and maintenance of epithelial barriers were modulated in the range of their dysregulation.

Results further substantiate the clinical data on STW5 and might pave the way for clinical use of multi-target agents like STW5 in the treatment of GERD, especially in patients not adequately controlled by PPIs.