Introduction
Natural products are typically characterized by their multitude of constituents addressing multiple targets in the organism. Their action has therefore been often postulated to be based on a multi drug/multi target action (1). This has been successfully proven for an herbal medicinal extract combination used in functional gastrointestinal diseases, STW 5 (2), as its action is based on very different effects in different regions of the stomach and the intestine (3). With a multiplicity of targets being the basis of its proven therapeutic efficacy and safety, synergy is assumed to be a key for its action.
Methods
As a model, rat and guinea pig small intestinal smooth muscle preparations, stimulated with ACh (4), or incubated with TNBS for inducing an inflammation (5), were used. STW 5 and its components, alone or in combinations, were tested. A Box-Behnken-Design and the isobologram method were used for analysis.
Results
The smooth muscle-relaxing effects of STW 5 were supra-additive in the model of ACh-induced contraction in comparison to the single components. In the TNBS-model, synergistic, additive as well as antagonistic effects were identified, depending from the combinations of extracts tested.
Discussion
Our results support the concept of a multi-target therapy, with synergy as a key factor. Further evidence for this concept is presently generated by modern gene expression profiling methods (6) giving a rationale for the good clinical efficacy and safety of natural products used in modern phytotherapy, and proven in modern clinical trials.
References
1. Wagner et al. 2006, Phytomedicine 13 SV:122; 2. Storr et al. 2016, Pharmakon 4:356; 3. Schemann et al. 2006, Phytomedicine 13 SV, 90; 4. Heinle et al. 2006, Phytomedicine 13 SV, 75; 5. Nieber et al. 2016, Neurogastroenterol Motil 8:83; 6. Ulrich-Merzenich et al. 2017. Gastroenterology 152:S308.