The multi‐herbal drug STW 5 (Iberogast^®) has prosecretory action in the human intestine

Abstract

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.

Stimulation of Murine Intestinal Secretion by Daily Genistein Injections: Gender-dependent Differences

“…Our data is consistent with other studies utilizing glibenclamide at similar concentrations in isolated rat distal colon [31], human intestinal epithelial cells [39] and isolated murine ascending colon [29]. Recent evidence suggests the importance of an alternative Cl -channel to CFTR that is present in intestinal epithelia which is regulated by a PKA-independent, Epac-mediated pathway [40].…”

Signaling mechanisms involved in the intestinal pro-secretory actions of hydrogen sulfide

“…To test the effects of the H 2 S donor NaHS on ion secretion in intact submucosa/mucosa preparations of guinea-pig and human intestine we employed Ussing chamber techniques (Easy Mount chambers, Physiologic Instruments, San Diego, CA, USA) as previously described in detail 12,23 . The area of the recording chamber was 0.5 cm 2 .…”

Complementary and Alternative Medicine for Gastroparesis

“…39 STW 5 may have other effects, including modulating intestinal afferent sensitivity as shown in male Wistar rats 40 and some of its components exert antispasmolytic, prosecretory, and anti-inflammatory effects in the small intestine and colon in animal models. 41,42 A randomized placebo-controlled trial using STW 5 in patients with functional dyspepsia for 8 weeks showed it to have a slightly better improvement in Gastrointestinal Symptom Score (GIS) compared with placebo with no difference in adverse effects. 43 Another randomized placebo double-blind study of patients with functional dyspepsia also documented improvement in the GIS in those randomized to STW 5, but no acceleration in gastric emptying in those with documented gastroparesis.…”