The multi-herbal drug STW 5 (Iberogast) has prosecretory action in the human intestine.
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.
Krueger
D
D
Department of Human Biology, Technische Universität München, München, Germany.
Gruber
L
L
Buhner
S
S
Zeller
F
F
Langer
R
R
Seidl
S
S
Michel
K
K
Schemann
M
M
D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*
D010936:Plant Extracts; C039964:iberogast