Elimination of undesirable modes of actions by combining different plant extracts: the example of STW5

The rational of combining different plant extracts is often questioned. The common argument for combinations is the elimination of adverse effects by the chosen combination partners. We investigated the capability of STW5, a combination of 9 different plant extracts (Iberis amara L., Menthae piperitae L., Chamomilla recutita (L.) Rauschert, Glycyrhiza glabra L., Angelica archangelica L., Carum carvi L., Silybium marianum (L.) Gaertn. Melissa officinalis L. and Chelidonium majus L.) to modulate interleukin 8 (IL-8). Il-8 is a small heparin binding protein mediating the activation and migration of neutrophils from blood into tissues. We selected IL-8 since we showed earlier its major involvement in reflux esophagitis [1], an indication for STW5. Synchronized HET1A cells were treated (18 hrs), alone or in presence of the pro-inflammatory capsaicin (80µM), with STW5 or its single extracts (4 concentrations). The experimental conditions did not influence cell viability (resazurin assay). The spontaneous release of IL-8 was 46.3 ± 4.8 pg/ml. The highest release of IL-8 was induced by the Iberis amara extract (IBE) (441 ± 177 pg/ml), whereas STW5 lead to releases up to 49.3 ± 4.2 pg/ml. Other extracts like Silybium marianum reduced releases up to 20.1 ± 8pg/ml. Capsaicin increased IL-8 release to 85.8 ± 1 4pg/ml (p < 0.005). Under this condition IBE stimulated an IL-8 release up to 625 ± 121 pg/ml. STW5 reducedIL-8 releases in the presence of capsaicin up to 33.7 ± 2 pg/ml. Thus Il-8 releases induced by the different plant extracts were apparently not simply additive. The chosen plant combination lead to a downregulation of Il-8. Cytokines are organized in networks with a significant measure of redundancy. They are important signal transducing molecules in the intestinal immune system which support the maintenance of physiological functions. Studies how plant extracts influence cytokine networks will improve our ability to rationally compose effective and safe plant combinations.

Acknowledgement: A. Shcherbakova was supported by the German Academic Exchange Service (DAAD). The study received research funds from the Steigerwald Arzneimittelwerk Gmb.

Keywords: IL-8, cytokine network, gastrointestinal diseases.

References:

[1] Abdel-Aziz H, Schneider M, Neuhuber W, Meguid Kassem A, Khailah S, Jürgen Müller J, Gamaleldeen H, Khairy A, Khayyal FM, Thomas Efferth T, Ulrich-Merzenich G. GPR84 and TREM-1 signaling contribute to the pathogenesis of reflux esophagitis. Mol Med 2015; 21: 1011 – 1014