title: Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed herbal combination STW 5 (Iberogast®) in rat small intestinal preparations.
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 A(2B)R mRNA, which was unaffected. STW 5 reversed these effects and enhanced A(2A)R expression above control levels. Radioligand binding assays confirm the affinity of STW 5 to the A(2A)R, and the A(2A)R 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 A(2A)R, which is involved in the anti-inflammatory action of STW 5. STW 6 did not contribute to adenosine A(2A)R-mediated anti-inflammatory effect of STW 5. Other signaling pathways could be involved in the mechanism of action of STW 6.
authors.affiliation: Löwen-Apotheke, Waldheim, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michael
authors.forename: Heba
authors.initials: H
authors.lastname: Abdel-Aziz
authors.forename: Dieter
authors.initials: D
authors.lastname: Weiser
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Olaf
authors.initials: O
authors.lastname: Kelber
authors.forename: Karen
authors.initials: K
authors.lastname: Nieber
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D007579:Jejunal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007583:Jejunum / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000502:physiology*; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; C039964:iberogast; D014302:Trinitrobenzenesulfonic Acid