Anti-inflammatory Effects of Herbal Preparations STW5 and STW5-II in Cytokine-Challenged Normal Human Colon Cells

Abstract

Inflammatory bowel diseases (IBD) are chronic relapsing intestinal disorders characterized by up-regulation of pro-inflammatory cytokines followed by invasion of immune cells to the intestinal lamina propria. Standard therapies consist of anti-inflammatory or immunosuppressive drugs. Since clinical efficiency is not satisfactory and the established drugs have massive side effects, new strategies to treat IBD are required. Herein, we investigate the protective effect of the fixed combination herbal preparations STW5 and STW5-II and the contribution of the corresponding single components in an in vitro inflammation model. The normal human colon epithelial cell line, NCM460, was treated with STW5, STW5-II or their single components for 4 h followed by experimental conditions comparable to induction of colitis. A pro-inflammatory cytokine cocktail consisting of TNF-α, IL-β, and IFN-γ was used to simulate inflammatory stimuli normally caused by immune cells. The effects on NCM460 cells were investigated by enzyme-linked immunoassay and Proteome Profiler®. Levels of IP-10, MCP-1, I-TAC, Groα, and IL-8 were elevated in chemokine-treated cells compared to untreated cells, but significantly reduced upon pretreatment with STW5 or STW5-II. However, the single compounds revealed only little effects on protein expression. Furthermore, we investigated the effect of both combination preparations on pro-inflammatory transcription factors of the STAT family using Western blot. In addition, we tested the effects on upstream MAPK p38. Both, STW5 and STW5-II did not show any effect on MAPK p38, but were effective in reducing phosphorylated levels of STAT1. In conclusion, both combination preparations act in an anti-inflammatory manner by influencing cytokine secretion via reduced activity of the JAK/STAT1 pathway. Relevant differences between STW5 and STW5-II were not found indicating similar efficacies.

Adhesion Properties of Food-Associated Lactobacillus plantarum Strains on Human Intestinal Epithelial Cells and Modulation of IL-8 Release

“…We investigated whether adhesive interaction of Lb. plantarum strains could modulate NCM460 IL-8 release after inflammation induced by a cytokine mixture (IL-1β, TNF-α, and INF-γ) that mimics inflammatory response in cell models ( Mueller et al, 2013 ; Schneider et al, 2016 ). Therefore, among all the potential induced cytokines that NCM460 cells can release, we focused on IL-8 that is considered one of the most effective neutrophil activator, widely used as an inflammatory marker in intestinal cell lines ( Noh et al, 2015 ; Schneider et al, 2016 ).…”

“…plantarum strains could modulate NCM460 IL-8 release after inflammation induced by a cytokine mixture (IL-1β, TNF-α, and INF-γ) that mimics inflammatory response in cell models ( Mueller et al, 2013 ; Schneider et al, 2016 ). Therefore, among all the potential induced cytokines that NCM460 cells can release, we focused on IL-8 that is considered one of the most effective neutrophil activator, widely used as an inflammatory marker in intestinal cell lines ( Noh et al, 2015 ; Schneider et al, 2016 ). Similar to previous studies, the treatment of intestinal cells with inflammatory cytokines led to a clear increase in IL-8 secretion ( Figure 8 ; Reilly et al, 2007 ; Ren et al, 2013 ; Schneider et al, 2016 ).…”

“…Briefly, NCM460 cells were pre-treated with Lb. plantarum cells suspensions (∼100 bacteria/cell) for 4 h and subsequently inflammation was induced for 24 h using a human cytokine mixture (IL-1β, TNF-α, and INF-γ) ( Schneider et al, 2016 ). After centrifugation, the supernatants were collected and analyzed following the manufacturer’s instructions.…”

“…Indeed, many probiotic products are used by healthy consumers, presuming that probiotics assumption can preserve their health, and potentially reduce the long-term risk of many diseases. Actually, in the last years, intestinal epithelial cell lines having a healthy phenotype, have been used to investigate adhesion and immunomodulation properties of potential probiotics ( Nissen et al, 2009 ; Cencic and Langerholc, 2010 ; Botta et al, 2014 ; Gorenjak et al, 2014 ), as well as anti-inflammatory effects of dietary adjuncts ( Schneider et al, 2016 ).…”

Mechanism of Action of STW 5 in Functional Dyspepsia and IBS: The Origin of Multi-Target

“…However, STW 5′s anti-inflammatory effects do not seem to be mediated by COX-inhibition, an effect that contributes to its mucosa-protective activity [12,23,29,30]. While all single extracts contributed to the overall anti-inflammatory effects of STW 5, the strongest actions were seen with bitter candytuft followed by Melissa (Fig.…”