Contribution of the components of STW 5 to its inhibitory effect on gene expression and release of the pro-inflammatory cytokine TNF-α

STW 5 (Iberogast®) is successfully used in the therapy of gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome (IBS). Pharmacological studies have demonstrated a multi-target effect of this fixed herbal combination. Actions on nerve, smooth muscle, epithelium and intestinal inflammation are revealed. Given that recent clinical data suggest an inflammatory etiology of IBS, the influence of STW 5 and its components on the production of the pro-inflammatory cytokine TNF-α was examined. The gene expression of TNF-a was determined in rat ileum preparations by realtime-RT-PCR. TNBS was used to induce inflammation. The release of TNF-α was measured in LPS-stimulated human monocytes using a commercially available ELISA. The TNBS-induced inflammation was accompanied by an increased TNF-α gene expression. STW 5 inhibited the increased gene expression and reduced significantly the release of TNF-α to 13% in LPS-stimulated monocytes, while having no effect in untreated cells. In further experiments the single herbal components of STW 5 were tested separately in concentrations equivalent to those in the combination. Caraway (Carum carvi L.), milk thistle (Silybum marianum L.), lemon balm (Melissa officinalis) and greater celandine (Chelidonium majus L.) had no effect on the TNF-α release. Bitter candytuft (Iberis amara L.), peppermint (Mentha piperita L.), chamomile (Matricaria recutita L.), liquorice (Glycyrrhiza glabra L.) and angelica (Angelica archangelica L.) reduced the TNF-α release, though less pronounced as compared to STW 5. The results indicate that a group of five components, including Iberis amara, contributes relevantly to the distinct effect of the herbal combination STW 5.