Mechanisms underlying the potential usefulness of STW 5 in reflux esophagitis

H Abdel-Aziz; G Ulrich-Merzenich; O Kelber; D Weiser; MT Khayyal

doi:10.1055/s-0032-1313241

Zeitschrift für Phytotherapie, Inhaltsverzeichnis

Mechanisms underlying the potential usefulness of STW 5 in reflux esophagitis

H Abdel-Aziz ¹^,², G Ulrich-Merzenich ³, O Kelber ², D Weiser ², MT Khayyal ⁴

¹Institute of Pharmaceutical Chemistry, University of Münster, Hittorfstr. 58–62, 48149Münster, Germany
²Scientific Dpt., Steigerwald Arzneimittelwerk GmbH, Havelstr. 5, 64295 Darmstadt, Germany
³Medizinische Poliklinik, University of Bonn, Wilhelmstr. 35–37, 53111 Bonn, Germany
⁴Dpt. of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt

Abstract

STW 5, a multi-component herbal preparation, was shown to relieve heartburn and concomitant reflux symptoms in patients with functional dyspepsia and to prevent inflammation in an acute model of reflux esophagitis (RE), without affecting the pH of the refluxate. The present study assesses the efficacy of STW 5 in a sub-chronic model of RE, and the underlying mechanisms both in vivo and in vitro. Rats were pretreated for 7d with STW 5 or omeprazole (as reference drug) before surgical induction of esophagitis. RE was achieved by ligation of the fore-stomach and covering the pylorus with a piece of Nelaton catheter. Rats were treated for a further 10d with the drugs and then sacrificed, their esophagi excised, weighed and evaluated macroscopically. Tissue homogenates were used for determination of cytokines using a cytokine array. Both STW 5 and omeprazole, improved body weight, tissue damage score and esophageal weight index to similar extents. However, STW 5 had a much more pronounced anti-inflammatory effect. As shown in the cytokine array, STW 5 inhibited the majority of the measured pro-inflammatory cytokines induced by surgical reflux, suggesting a direct anti-inflammatory and/or mucosa protecting action.

Since recent evidence indicates that the mucosal damage observed in GERD is due to release of inflammatory mediators from mucosa and sub-mucosa, the effects of STW 5 on cytokine release from the normal human esophageal cell-line HET-1A in response to stimulation with chenodeoxycholic acid (CDCA) was assessed. Incubation of cells with CDCA caused marked release of CD40-ligand, IFN-γ, IL-1ra, IL-6, IL-8 and IL-23, which were all inhibited by co-incubation with STW 5 (0,3–10µl/ml) as assessed with a cytokine array and confirmed by ELISA, without affecting cell viability.

The present findings suggest that multi-target anti-inflammatory drugs like STW 5 might present an alternative/additional treatment option for GERD patients not responding adequately to PPIs.

Danksagung: Wir danken Prof. E.J. Verspohl für die Möglichkeit, seine Labore zu nutzen und für die Unterstützung bei der Versuchsplanung und -durchführung.