STW5 is a herbal multicomponent mixture which is recommended in the management of functional dyspepsia. It is a combination of 9 different plant extracts (Iberis amara (L.), Menthae piperitae (L.) Chamomilla recutita (L.), Glycyrhiza glabra (L.), Angelica archangelica (L.), Carum Carvi (L.), Silybium marianum (L.) Gaertn. Melissa officinalis (L.) und Chelidonium majus (L.). We reported earlier that STW5 targets the fatty acid receptor GPR84 [1], receptors involved in pain sensing (ASIC4, 5-HT) and multiple chemokine families on genome and proteome levels. Based on these data we proposed IL-8 and the TREM-1 signaling pathway to play an important role in the pathogenesis of GERD. We therefore investigated the influence of STW5 and its component on the IL-8 release in human esophageal epithelial cells (HET1A) alone or in combination and under stimulation of Capsaicin (80µM). As reported [2] the selected plant compostion in STW5 lead to a downregulation of Il-8. But the Il-8 releases provoked by the different plant extracts were not simply additive. For the determination of synergistic, additive and antagonistic effects of the different plant extracts in combination we used the Chou-Talalay method and determined the Combination index (CI). The CI values of the triple combinations tested ranged from high synergies (CI<0.3) up to antagonism (CI:480). Within the combination Menthae piperitae (L.) and Silybium marianum (L.) were identified as the most effective combination partners in the inhibition of IL-8 releases. We further investigated the Ca-release in human intestinal smooth muscle cells (HISMC). Here STW5 did induce an increase in the Ca-release. In this cellular model a single plant extract – Mellissa officinalis (L.)- was identified to provoke the increased Ca-release. The identification of multi-target and synergistic effects in phytopharmaceuticals will improve our ability to rationally compose effective and safe plant combinations.
[1] Abdel-Aziz H et al. Mol Med 2015;21:1011-1024.
[2] Ulrich-Merzenich G et al. Planta medica 2016;81(S01):S1-S381.