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Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed herbal combination STW 5 (Iberogast®) in rat small intestinal preparations

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Abstract

STW 5 (Iberogast®), an established herbal combination, was effective in randomized, double blind clinical studies in functional dyspepsia and irritable bowel syndrome. Since STW 5 was found to influence intestinal motility and has anti-inflammatory properties, this study investigated the expression of adenosine receptors and characterized their role in the control of the anti-inflammatory action of STW 5 and its fresh plant component STW 6 in inflammation-disturbed rat small intestinal preparations. The inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 0.01 M). The effects of coincubation with selective receptor agonists and antagonists, STW 5, STW 6, or combinations of these compounds on acetylcholine (ACh)-evoked contraction of ileum/jejunum preparations were tested. Adenosine receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). In untreated preparations, RT-PCR revealed the presence of all adenosine receptor subtypes. Suppressed expression was detected for all subtypes in inflamed tissues, except for A2BR mRNA, which was unaffected. STW 5 reversed these effects and enhanced A2AR expression above control levels. Radioligand binding assays confirm the affinity of STW 5 to the A2AR, and the A2AR antagonist was able to prevent the effect of STW 5 on TNBS-induced attenuation of the ACh contraction. Our findings provide evidence that STW 5, but not STW 6 interacts with A2AR, which is involved in the anti-inflammatory action of STW 5. STW 6 did not contribute to adenosine A2AR-mediated anti-inflammatory effect of STW 5. Other signaling pathways could be involved in the mechanism of action of STW 6.

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Authors and Affiliations

  1. Löwen-Apotheke, Waldheim, Germany

    Sebastian Michael

  2. Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

    Heba Abdel-Aziz, Dieter Weiser & Olaf Kelber

  3. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany

    Christa E. Müller

  4. Institute of Pharmacy, Pharmacology for Natural Sciences, University of Leipzig, Talstrasse 33, 04103, Leipzig, Germany

    Karen Nieber

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  1. Sebastian Michael
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Michael, S., Abdel-Aziz, H., Weiser, D. et al. Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed herbal combination STW 5 (Iberogast®) in rat small intestinal preparations. Naunyn-Schmiedeberg's Arch Pharmacol 385, 411–421 (2012). https://doi.org/10.1007/s00210-011-0714-y

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