Planta Med 2007; 73 - P_036
DOI: 10.1055/s-2007-986818

Characterisation of anti-inflammatory effects of STW5 and STW6 on rat small intestine in vitro: Involvement of adenosine A2A receptors

K Nieber 1, S Michael 1, CE Müller 2, O Kelber 3
  • 1Institute on Pharmacy, University of Leipzig, Talstr. 33, D-04103 Leipzig, Germany
  • 2Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
  • 3Steigerwald Arzneimittel GmbH, Havelstr. 5, D-64295 Darmstadt, Germany

The phytotherapeutic agent STW 5 is successfully used in the therapy of motility disorders but its effect on inflammatory processes in the gut remains unclear. The aim of the present study was to compare possible anti-inflammatory properties of STW 5 and its lead component, STW 6 (Iberis amara fresh plant extract) on the rat small intestine in vitro and to study the involvement of adenosine A2A receptors (A2AR). The experiments were performed on isolated ileum/jejunum preparations in conformity with the German Guidelines for Animal Care. The inflammation was induced with 2,4,6 trinitrobenzolsulfonic acid (TNBS, 0.01M). The ACh-evoked (1 mM) contractions were measured isometrically. TNFα-mRNA was assayed using quantitative RT-PCR with SYBR® Green as detecting agent. Morphological changes were visualized after van Gieson staining. Radioligand binding assays were carried using [3H] CGS21680 as radioligand. Preincubation of the tissue preparations with TNBS (30min) resulted in an inhibition of the ACh-evoked contraction. STW 5 (64–512µg/ml) and STW 6 (3–24µg/ml) prevented this inhibition concentration dependently, when they were coapplied with TNBS. TNBS induced morphological changes of the smooth muscular layers and the mucosa. The coincubation of STW 5 and STW 6, respectively, resulted in more intact mucosal and muscular layers. The protective effects of the two herbal preparations on contractile and morphological disturbances were blocked by the A2AR antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC 0.2µM). To evaluate an anti-inflammatory mechanism TNF-α mRNA and its LPS-stimulated releases from monocytes were investigated. STW 5 but not STW 6 diminished the TNBS-induced increase of TNFα-mRNA level and inhibited the LPS-stimulated release. These effects were also blocked by CSC (0.2µM). Radioligand binding assays confirmed the affinity of STW 5 to the A2AR, whereas STW 6 did not bind. The results indicate that STW 5 and STW 6 act anti-inflammatory by direct or indirect activation of A2AR. The involvement of other adenosine receptors subtypes cannot be excluded, especially in the action of STW 6.