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.