Simmen U, Kelber O, Okpanyi S N, Jaeggi R, Bueter B, Weiser D
Institute of Pharmaceutical Biology, University of Basel, Switzerland.
Phytomedicine. 2006;13 Suppl 5:51-5. doi: 10.1016/j.phymed.2006.03.012. Epub 2006 Sep 14.
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).
对固定草药复方产品STW 5（伊贝戈斯特）开展的临床研究表明，在功能性消化不良（FD）和肠易激综合征（IBS）等功能性胃肠疾病中，其疗效与甲氧氯普胺（5 - HT(3)拮抗剂）和西沙必利（5 - HT(4)激动剂）相当。由于已知血清素（5 - HT(3)和5 - HT(4)）以及毒蕈碱M(3)受体在FD和IBS的病因中起核心作用，因此对STW 5中所含提取物及其几种植物化学成分进行了体外研究，以考察它们与肠道这些受体的结合亲和力。STW 5分别抑制(3)H - GR113808和(3)H - 4 - DAMP与5 - HT(4)和M(3)受体的结合，其效力比(3)H - GR65630与5 - HT(3)受体的结合约强10倍。STW 5的IC(50)值对应于1:1000的提取物稀释度（M(3)结合）和1:2000的提取物稀释度（5 - HT(4)结合）。此外，STW 5还能有效抑制与阿片受体的结合，IC(50)值为1:2000。在STW 5所含的9种草药提取物中，碎米荠（ Iberis amara）的新鲜植物提取物选择性抑制与M(3)受体的结合，而白屈菜和洋甘菊花的乙醇提取物对5 - HT(4)具有选择性，甘草根提取物对5 - HT(3)受体具有选择性。与重组人5 - HT(3)、5 - HT(4)和M(3)受体的结合亲和力在性质上与相应的肠道受体相似。苄基异喹啉生物碱黄连素对5 - HT(4)和M(3)结合有显著抑制作用，IC(50)值分别为40 ng/ml（100 nM）和200 ng/ml（500 nM），但仅微量存在于白屈菜提取物中，因此对于白屈菜提取物也可假定几种植物化学成分具有协同作用。这些体外数据表明，5 - HT(4)（程度较轻的5 - HT(3)）、毒蕈碱M(3)和阿片受体是STW 5（伊贝戈斯特）治疗FD和IBS的靶点。
