Elsevier

Phytomedicine

Volume 13, Supplement 1, 24 November 2006, Pages 20-35
Phytomedicine

The active components and the pharmacological multi-target principle of STW 5 (Iberogast®)

https://doi.org/10.1016/j.phymed.2006.07.001Get rights and content

Abstract

The therapeutic equivalence of the multi-herbal drug combination STW 5 (Iberogast ®) with two synthetic standard drugs can be explained by an additive or overadditive pharmacological synergism. A review of the different chemical constituents contained in this fixed combination of nine herbal drug extracts and their dominant mechanisms of action shows that they correlate very well with the clinically relevant overall pharmacological profile of the multi-herbal drug combination. This comprises modulatory effects on gastro-intestinal motility, anti-inflammatory action, inhibitory effects on gastric acid production and anti-oxidative and radical-inhibiting properties. As a multi-drug preparation with a multitude of therapeutic targets relevant in functional gastrointestinal diseases, its pharmacological profile of action in accordance with the multi-target principle.

Introduction

A herbal medicinal preparation derived from several herbal plant extracts contains a large number of secondary phytochemical compounds, which is considerably higher than that of an extract derived from a single drug. Such a combination of many constituents was therefore to be expected for STW 5 (Iberogast®) containing extracts from nine herbal drugs (Fig. 1).

As in earlier times only those compounds present in higher concentrations in a drug could be identified, research focussed on these main constituents with regard to chemical standardisation and pharmacological testing, even if it was not sure whether they included the main therapeutically relevant active ingredients of the extract. So they often could be only described as marker substances. Nowadays, it is known from numerous preclinical and clinical studies carried out with plant extracts that an entire extract in most cases has a better efficacy than one single main constituent isolated from such an extract. So it can be concluded, that in the pharmacological overall effects and the therapeutic efficacy of multi-extract preparations also numerous other constituents must be involved synergistically. Experimental studies with different combinations of active ingredients have demonstrated that such synergistic effects can be additive or superadditive (Wagner, 2006). The assumption that a superadditive effect is involved in the case of STW 5 is supported by the fact that the multi-extract preparation showed therapeutic equivalence in comparative studies with two synthetic standard preparations (Nicolay, 1984; Rösch et al., 2002, Rösch et al., 2006).

This result can only be explained when several active components of the preparation are acting synergistically and contributing to the overall effect and if it can be assumed that these individual components act on different pharmacological targets (Wink, 2005). At present, it is in detail not understandable how these synergistic effects arise in detail. Therefore, it is also not possible to theoretically predict the expected overall effect of a herbal drug or combination of drugs based on the known effects of distinct substances in the entire preparation. Also the rule applies that the effect of the entire preparation is greater than the sum of the effects of each single distinct substances. Future research on the reasons for such synergistic effects will at first have to elucidate what pharmacological and therapeutic contributions each distinct active component of an extract preparation provides and, secondly, which chemical substances or substance groups from the extracts are responsible for which specific pharmacological effects. This means to relate the pharmacological profile of an extract or a combination of extracts to the multicausality of a disease state, which is a confirmation of the multi-target principle at the same time. When these different single effects of the preparation are known, this has to be standardised in order to ensure reproducible pharmacological and therapeutic results. Concerning the combination product STW 5 the different extracts contained in the combination must be standardised in terms of their pharmacologically relevant components and properties. This strategy has been employed in the pharmacological research on STW 5 and on the extracts contained.

As a result of these investigations, a total of five predominating pharmacological actions were determined, as is shown in the following single contributions in this supplementary volume. All these actions show a direct therapeutic relationship to the symptoms of functional gastro-intestinal diseases.

They include

  • a tonicising, prokinetic action,

  • a gastro-intestinal spasmolytic action,

  • an anti-secretory action,

  • an anti-inflammatory action and

  • an anti-oxidative as well as a radical-inhibiting action.

Extensive literature research was carried out (e.g. via MEDLINE and EMBASE) to list the known chemical constituents of the drugs from STW 5 (Table 1) and to relate them to three main pharmacological actions (Table 2, Table 3, Table 4).

Section snippets

Constituents and substance classes from the herbal drugs in STW 5

All herbal drugs contained in STW 5 have been very well investigated analytically. So, as was to be expected, a large number of secondary chemical constituents could be identified for each of the nine drugs. A total of more than 350 distinct chemical compounds, including about 200 with known pharmacological activity, were found and classified into substance classes. Table 1 lists substance classes and numbers of chemical compounds, which have been identified for the different drugs, and

Pharmacological actions of phytochemical compounds from the drugs contained in STW 5

The structured evaluation of the pharmacological literature yielded numerous information concerning the effects of the individual substances. The following main pharmacological effects were found:

  • Motility modulating effects (Table 2).

  • Anti-inflammatory effects (Table 3).

  • Anti-oxidative and radical-inhibiting effects (Table 4).

These effects are dealt with in detail in the following. Only those substances are included in the Table 2, Table 3, Table 4, for which published data on the appropriate

Modulating effects on gastro-intestinal motility

Motility modulating effects have been reported from in vitro studies from a total of at least 7 substance classes. Spasmolytic and antispasmodic effects are subsumed under this topic.

Volatile oil (as drug-specific oils, for 5 drugs), sesquiterpenes with subclasses (for 5 drugs), coumarins (for 2 drugs), flavonoids with subclasses (for 3 drugs), monoterpenes (for 5 drugs) and phenol carboxylic acids (for 4 drugs) can be given as predominating substance classes from STW 5 known to have effects on

Anti-inflammatory effects

Anti-inflammatory or antiphlogistic properties have been reported from in vitro and in vivo studies from a total of at least 7 substance classes.

Flavonoids with subclasses (for 5 drugs), sesquiterpenes with subclasses (for 5 drugs), coumarins (for 4 drugs), monoterpenes (for 4 drugs) and phenol carboxylic acids (for 4 drugs) have to be mentioned as the predominating substance classes in several drugs. In addition, there are alkaloids and cucurbitacines for 1 drug in each case. Other substance

Anti-oxidative and radical inhibiting effects

Anti-oxidative or radical inhibiting effects were reported from experimental in vitro studies for a total of about 7 substance classes. These effects are of possible relevance to anti-ulcerative, ulcer-protective and anti-inflammatory effects.

As expected, the flavonoids with subclasses (for 7 drugs) and the phenol carboxylic acids (for 4 drugs) are the predominating substance classes in several drugs. Furthermore, monoterpenes (for 2 drugs), coumarins (for 4 drugs) and volatile oil (for 2

Summary and conclusion

STW 5 (Iberogast®) is a combination of nine herbal drugs containing many different phytochemical substances. The properties of similarly acting substance groups complement each other and contribute all to varying degrees to the overall pharmacological activity profile of the combination.

The superior adaptation of the profile of action of the combination to its therapeutic indication is the supposed cause for the advantages in comparison to a mono preparation. While a single extract can be

Acknowledgements

Thanks to Mrs. Diana Long for her valuable assistance by the responsible administration of the literature database.

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