Krueger D, Gruber L, Buhner S, Zeller F, Langer R, Seidl S, Michel K, Schemann M
Department of Human Biology, Technische Universität München, München, Germany.
Neurogastroenterol Motil. 2009 Nov;21(11):1203-e110. doi: 10.1111/j.1365-2982.2008.01242.x. Epub 2009 Jan 30.
There is growing evidence that STW 5 (Iberogast), fixed combination of hydroethanolic herbal extracts), besides being effective in functional dyspepsia, also improves symptoms in irritable bowel syndrome (IBS). Clinical data indicate that modulation of mucosal secretion is a promising approach to treat intestinal disorders associated with IBS. We therefore explored the effect of STW 5 on secretion in the human intestine and the mechanisms by which it acts. The Ussing chamber technique was used to measure mucosal secretion in human intestinal mucosa/submucosa preparations and in human epithelial cell line T84. In addition, we recorded STW 5 effects on human enteric neurons with voltage sensitive dye imaging. In human tissue and T84 cells STW 5 induced a dose-dependent increase in ion secretion that was significantly reduced by the Na-K-Cl cotransporter blocker bumetanide, the adenylate cyclase inhibitor MDL-12 330, the non-specific and selective cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors glibenclamide and CFTR(inh)-172, respectively, and the blocker of calcium dependent Cl(-) channels (ClCa) SITS (4-acetamido-4-isothiocyanatostilbene-2,2-disulphonic acid). It was unaffected by amiloride, a blocker of epithelial Na(+) channels. In human tissue, the nerve blocker tetrodotoxin significantly suppressed the STW 5 response. STW 5 evoked an increased spike discharge in 51% of human submucous neurons. Results suggest that STW 5 is a secretogogue in the human intestine by direct epithelial actions and through activation of enteric neurons. The prosecretory effect is due to increased epithelial Cl(-) fluxes via CFTR and Ca-dependent ClCa channels. STW 5 may be a novel option to treat secretory disorders associated with IBS and constipation.
越来越多的证据表明，STW 5（伊贝戈斯特，一种水醇性草药提取物的固定组合）除了对功能性消化不良有效外，还能改善肠易激综合征（IBS）的症状。临床数据表明，调节黏膜分泌是治疗与IBS相关的肠道疾病的一种有前景的方法。因此，我们探究了STW 5对人体肠道分泌的影响及其作用机制。采用Ussing chamber技术测量人体肠黏膜/黏膜下层制剂和人上皮细胞系T84中的黏膜分泌。此外，我们用电压敏感染料成像记录了STW 5对人体肠神经元的影响。在人体组织和T84细胞中，STW 5诱导离子分泌呈剂量依赖性增加，而钠-钾-氯共转运体阻滞剂布美他尼、腺苷酸环化酶抑制剂MDL-12 330、非特异性和选择性囊性纤维化跨膜电导调节因子（CFTR）抑制剂格列本脲和CFTR(inh)-172以及钙依赖性Cl(-)通道（ClCa）阻滞剂SITS（4-乙酰氨基-4-异硫氰酸根合芪-2,2-二磺酸）分别显著降低了这种增加。它不受上皮钠(+)通道阻滞剂氨氯吡咪的影响。在人体组织中，神经阻滞剂河豚毒素显著抑制了STW 5反应。STW 5使51%的人体黏膜下神经元的动作电位发放增加。结果表明，STW 5通过直接作用于上皮细胞和激活肠神经元而成为人体肠道中的促分泌剂。促分泌作用是由于通过CFTR和钙依赖性ClCa通道增加了上皮Cl(-)通量。STW 5可能是治疗与IBS和便秘相关的分泌性疾病的一种新选择。
