Elucidation of multi-target mechanisms of STW5-II on functional dyspepsia

Introduction STW 5-II, a combination of six plant extracts (Iberis amara L., Mentha piperita L., Matricaria chamomilla L., Glycyrrhiza glabra L., Carum carvi L., Melissa officinalis L.), is indi-cated for the treatment of Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS) symptoms in Germany. Native compounds of these extracts have been previously identified by LC/MS. Objective: FD gene targets for the native compounds in STW 5-II were predicted followed by wet lab validations to characterize effects of STW5-II and its single herbs.

Methods: Four databases were screened to identify gene targets involved in FD. Compound-target networks for FD were constructed to elucidate relationships between native compounds and FD targets. NCM460 colon cells were treated with STW 5-II, its individual herbs, or omeprazole. Gene expression (GE) analyses (deep sequencing) and RT-PCR were performed.

Results 96 genes were predicted as potential targets with AKT1, NOS3, HSP90A, TRPV and SMADs among the most common ones. In silico data were supported by GE-data (AKT1: 3.7fold(f); HSP90AA: 11.3f, TRPV3: 0.63 f, SMAD3: 5.1f (p<0.01). RT-PCR confirmed regulations of AKT1, NOS3 and SMAD3 by STW 5-II. GO and reactome pathway analyses indicate, among others, significant upregulations of cell motility, epithelium development and lipid metabolism by STW 5-II. The individual herbs in STW 5-II contributed differentially to its overall activity, justifying the differential role of the six herbs in targeting different pathways in FD pathogenesis.

Conclusion In silico and in vitro studies confirmed that STW 5-II is a multi-target herbal formula acting on relevant targets of FD. Combinations of in silico and in vitro studies are useful to elucidate the complex molecular mechanisms of FD.

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Artikel online veröffentlicht:
13. Dezember 2021