Elsevier

Phytomedicine

Volume 13, Supplement 1, 24 November 2006, Pages 90-99
Phytomedicine

Region-specific effects of STW 5 (Iberogast®) and its components in gastric fundus, corpus and antrum

https://doi.org/10.1016/j.phymed.2006.03.020Get rights and content

Abstract

Functional dyspepsia (FD) is a disorder that involves impaired gastric accommodation, antral hypomotility, and upper abdominal pain. The herbal drug STW 5 (Iberogast®) is used to successfully treat FD patients. Here, we report in vitro data revealing the mode of action of STW 5 and its individual herbal extracts on gastric motility. STW 5 evoked a relaxation of the proximal stomach but increased antral motility. Both effects are myogenic. The extracts of Angelica root, chamomile flower and liquorice root mimicked the inhibitory effects in the proximal stomach whereas the extracts of greater celandine herb, Melissa leaf, caraway fruit and bitter candy tuft increased motility of the proximal stomach. All extracts increased motility in the antrum comparable to the effects of STW 5. We conclude that the differential effects of STW 5 on proximal and distal stomach motor activity are not caused by solely spasmolytic or anti-spasmolytic effects of the individual components. It is suggested that the individual extracts target transduction mechanisms that are specifically expressed in the proximal vs. distal stomach. We present a rationale for the differential effect of STW 5 which is a result of the combined actions of its individual components and reason that the inhibitory effects in the proximal and the excitatory effects in the distal stomach may contribute to symptom relief in FD patients treated with STW 5 (Iberogast®).

Introduction

Functional dyspepsia (FD) – also known as “non-ulcer dyspepsia” – is amongst the most commonly seen functional gastrointestinal disorders (Koloski et al., 2002). It is characterized and defined by upper gastrointestinal symptoms-like heartburn, dyspepsia, fullness in the upper abdomen, early satiety, bloating, epigastric pain, or nausea and vomiting which occur in the absence of a detectable organic cause. Even though the origin of symptoms in FD remains relatively poorly defined, the diagnosis is mainly based on symptomatology and the clinical picture (Malfertheiner et al., 2001; Talley et al., 1998). It has been proposed to subdivide FD into three types, namely ulcer-like dyspepsia, dysmotility-like dyspepsia and unspecified dyspepsia which is merely based on symptomatology. With respect to pathophysiology, it has been suggested that dysmotility-like dyspepsia reflects impaired gastric relaxation together with antral hypomotility and abnormal gastric emptying (Stanghellini et al., 1996; Tack et al., 1998; Troncon et al., 1994, Troncon et al., 1995), and it has been subsequently recommended to preferentially treat dysmotility-like dyspepsia with gastroprokinetics and ulcer-like dyspepsia with acid-suppressive substances (Fisher and Parkman, 1998; Talley et al., 1998). However, the optimum treatment of FD is uncertain and the beneficial effect of most drugs is relatively small (Moayyedi et al., 2003). Moreover, many patients need to take their medication on a long-term basis to achieve symptomatic relief. Particularly herbal preparations are appealing to many patients because they are perceived as “natural” and hence harmless (Stickel et al., 2003), as well as relatively inexpensive. The therapeutic efficacy of herbal drug preparations to ameliorate dyspeptic symptoms in FD patients has been repeatedly demonstrated in prospective, placebo-controlled clinical trials (Madisch et al., 2001; Gundermann et al., 2003; Holtmann et al., 2003a, Holtmann et al., 2003b, Holtmann et al., 2004; Rösch et al., 2006) and in one study, it was even found that the herbal multi-compound preparation STW 5 (Iberogast®, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) had equivalent efficacy as the well-characterized prokinetic synthetic drug cisapride (Allescher et al., 2001; Rösch et al., 2002).

STW 5 is a fixed combination of hydroethanolic herbal extracts from bitter candy tuft (STW 6), peppermint leaf (STW 5-KII), chamomile flower (STW 5-KIII), liquorice root (STW 5-KIV), Angelica root (STW 5-KV), caraway fruit (STW 5-KVI), milk thistle fruit (STW 5-KVII), Melissa leaf (STW 5-KVIII), and greater celandine herb (STW 5-KIX) each of which is reported to have multiple pharmacological properties relevant for gastrointestinal pathophysiology (Saller et al., 2002).

In contrast to the gastroprokinetic cisapride, the effects of STW 5 on gastric motility have been largely unknown. Therefore, the present study was designed to investigate these effects as well as the contribution of the individual components of STW 5 to the observed phenomena.

Section snippets

In vitro studies of gastric motility

Throughout these studies, we have used isometric tension transducers to record the in vitro motility of muscle strip preparations from the entire guinea pig stomach which were cut either along the circular or the longitudinal muscle axis of fundus, corpus and antrum (Hohenester et al., 2004).

In all experiments, changes in muscle tension were calculated in comparison to pre-treatment baseline tension and expressed as mN. Treatment groups were compared using paired Student's t-tests and

How do the STW 5 effects relate to the action of its individual components?

We have provided evidence that the herbal compound drug STW 5 (Iberogast®) has profound, yet differential effects on gastric motility. In our experimental set-up, STW 5 significantly and dose-dependently decreased muscle tone in the gastric fundus and corpus while it enhanced antral contractility. Furthermore, we have found that three out of the 9 extracts constituting STW 5 closely mimicked the inhibitory effects of STW 5 on muscle tone in the proximal stomach, namely angelica root extract,

Acknowledgement

This study was supported by Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.

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