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  • Title: Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors.
    Author: Simmen U, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D.
    Journal: Phytomedicine; 2006; 13 Suppl 5():51-5. PubMed ID: 16973340.
    Abstract:
    Clinical studies with the fixed herbal combination product STW 5 (Iberogast) have indicated an efficacy comparable to metoclopramide (5-HT(3) antagonist) and cisapride (5-HT(4) agonist) in functional gastro-intestinal diseases like functional dyspepsia (FD) and irritable bowel syndrome (IBS). Since serotonin (5-HT(3) and 5-HT(4)) and muscarinic M(3) receptors are known to play a central role in the etiology of FD and IBS, the extracts contained in STW 5 and several of their phytochemical components were studied in vitro for binding affinities to these receptors of the intestine. STW 5 inhibited the binding of (3)H-GR113808 and (3)H-4-DAMP to 5-HT(4) and M(3) receptors, respectively, about 10 times more potently than the binding of (3)H-GR65630 to 5-HT(3) receptors. IC(50) values for STW 5 did correspond to extract dilutions of 1:1000 (M(3) binding) and 1:2000 (5-HT(4) binding). In addition, STW 5 also potently inhibited the binding to opioid receptors with an IC(50) value of 1:2000. Of the nine herbal extracts contained in STW 5, the fresh plant extract of bitter candy tuft (Iberis amara) selectively inhibited binding to M(3) receptors, while ethanolic extracts of celandine herb and chamomile flower were selective to 5-HT(4), and liquorice root to 5-HT(3) receptors. Binding affinities to human recombinant 5-HT(3), 5-HT(4) and M(3) receptors were qualitatively similar to those of the corresponding intestinal receptors. The benzylisoquinoline alkaloid berberine had significant inhibitory action on 5-HT(4) and M(3) binding, showing IC(50) values of 40 ng/ml (100 nM) and 200 ng/ml (500 nM), respectively, but is present in the extract of celandine herb only in traces, so that also for the celandine extract a cooperative effect of several phytochemical constituents can be assumed. These in vitro data indicate that 5-HT(4) (to a lesser degree 5-HT(3)), muscarinic M(3), and opioid receptors represent target sites for the treatment of FD and IBS with STW 5 (Iberogast).
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