The active components and the pharmacological multi-target principle of STW 5 (Iberogast®)
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
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a tonicising, prokinetic action,
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a gastro-intestinal spasmolytic action,
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an anti-secretory action,
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an anti-inflammatory action and
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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:
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Motility modulating effects (Table 2).
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Anti-inflammatory effects (Table 3).
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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.
References (176)
Functional dyspepsia—a multi-causal disease and its therapy
Phytomedicine
(2006)- et al.
Spasmolytic and tonic effect of lberogast (STWS) in intestinal smooth muscle
Phytomedicine
(2006) - et al.
Antioxidant effect of flavonoids after ascoroate/Fe(2+)induced oxidative stress in cultured retinal cells
Biochem. Pharmacol.
(2001) - et al.
Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid
J. Ethnopharmacol.
(2001) - et al.
Anti-inflammatory activity of D-002: an active product isolated from beeswax
Prostaglandins Leukot. Essent. Fatty Acids
(1998) - et al.
Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells
Life Sci.
(1996) - et al.
Rosmarinic acid: a new inhibitor of complement C3-convertase with anti-inflammatory activity
Int. J. Immunopharmacol.
(1988) - et al.
An antioxidant sinapic acid ester isolated from Iberis amara
Fitoterapia
(2000) - et al.
Licorice extract and its major polyphenol glabridin protect low-density lipoprotein against lipid peroxidation: in vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein-deficient mice
Am. J. Clin. Nutr.
(1997) - et al.
Antioxidative properties of the gastrointestinal phytopharmaceutical remedy STW 5
Phytomedicine
(2006)
Anti-inflammatory activity of taxifolin
Jpn. J. Pharmacol.
Pharmacological effects of selected flavonoids on rat isolated ileum: structure–activity relationship
Gen. Pharmacol.
Intestinal spasmolytic effects of STW 5 (Iberogast) and its components
Phytomedicine
Ursolic acid of Origanum majorana L. reduces a beta-induced oxidative injury
Mol. Cells
Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana
Cancer Lett.
Mechanisms involved in the gastro-protective effect of STW 5 (Iberogast) and its components against ulcers and rebound activity
Phytomedicine
Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens
Eur. J. Pharmacol.
Glycosides and xanthine oxidase inhibitors from Conyza bonariensis
Phytochemistry
Antioxidant activity of polyphenolics in diets: rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen
Biochim. Biophys. Acta
Pharmacology of oleanolic acid and ursolic acid
J. Ethnopharmacol.
Effects of furocoumarins from Cachrys trifida on some macrophage functions
J. Pharm. Pharmacol.
Pharmacological investigations on camomile constituents, V: investigations of the spasmolytic action of camomile constituents and Kamillosan on isolated guinea pig ileum
Planta Med.
Pharmacological activity of coumarins isolated from Afraegle paniculata; Part II
West Afr. J. Pharmacol. Drug Res.
Study of antimicrobial activity of chamomile oil
Planta Med.
Kamille: pharmakologie der kamille und ihrer inhaltsstoffe
Deut. Apotheker. Zeitung
Mechanismus der antiphlogistischen Wirkung von Kamillenextrakten- und Inhaltsstoffen
Deut. Apotheker. Zeitung
Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins
J. Agric. Food Chem.
Polyphenole flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis
Atherosclerosis
Effects of 7-hydroxycoumarin (umbelliferone) on isolated perfused and ischemic-reperfused rat heart
Arzneim-Forsch.
Protective effect of oleanolic acid and ursolic acid against lipid peroxidation
Biochem. Int.
Short-term toxicity studies of sanguinarine and of two alkaloid extracts of Sanguinaria canadensis L.
J. Toxicol. Environ. Health
HagerROM. Hagers Handbuch der Drogen und Arzneistoffe
Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes
Pharmacol. Res.
The effect of the phenolic antioxidant ferulic acid on the oxidation of low-density lipoprotein depends on the pro-oxidant used
Free Radic. Res.
Spasmolytische Wirkung ätherischer Öle
Z. Phytother.
Glycyrrhetinic acid, leucocytes and prostaglandins
J. Pharm. Pharmacol.
Chamomilla
Antinociceptive and anti-oedematogenic properties of astilbin, taxifolin and some related compounds
Arzneim-Forsch.
Structure–activity relationship of coumarins in xanthine oxidase inhibition
Anticancer Res.
Anti-inflammatory and analgesic activities from roots of Angelica pubescens
Planta Med.
Radical-scavenging activities of citrus essential oils and their components: detection using 1,1-diphenyl-2-picrylhydrazyl
J. Agric. Food Chem.
Isolation and structure elucidation of radical scavengers from Thymus vulgaris leaves
J. Nat. Prod.
Effect of silymarin on different acute inflammation models and on leukocyte migration
J. Pharm. Pharmacol.
Pharmacologic study of essential oils: antispasmodic activity of fifty samples
Plantes Med. Phytother.
A new method to demonstrate the anti-inflammatory action of azulene
Arzneim-Forsch.
Lokale antiphlogistische Wirkung der Kamillen-Flavone
Deut. Apotheker. Zeitung
Influence of gamma-irradiation and microwaves on the antioxidant property of some essential oils
Int. J. Food Sci. Nutr.
Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens
J. Pharm. Pharmacol.
Inhibition of sheep platelet arachidonate metabolism by flavonoids from Spanish and Indian medicinal herbs
Pharmazie
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A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats
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