Anti-inflammatory and tight junction protective activity of the herbal preparation STW 5-II on mouse intestinal organoids

Background - Irritable bowel syndrome (IBS) is a functional bowel disorder, in which recurrent abdominal pain is associated with defecation or a change in bowel habits. STW 5-II is a combination of six medicinal herbs with a clinically proven efficacy in managing IBS. - Aim - This study aims to esta...

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Main Authors: Elbadawi, Mohamed (Author) , Ammar, Ramy M. (Author) , Aziz-Kalbhenn, Heba (Author) , Rabini, Sabine (Author) , Klauck, Sabine (Author) , Dawood, Mona (Author) , Saeed, Mohamed E M (Author) , Kampf, Christopher J. (Author) , Efferth, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 6 May 2021
In: Phytomedicine
Year: 2021, Volume: 88, Pages: 1-17
ISSN:1618-095X
DOI:10.1016/j.phymed.2021.153589
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.phymed.2021.153589
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0944711321001318
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Author Notes:Mohamed Elbadawi, Ramy M. Ammar, Heba Aziz-Kalbhenn, Sabine Rabini, Sabine M. Klauck, Mona Dawood, Mohamed E M Saeed, Christopher J. Kampf, Thomas Efferth

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520 |a Background - Irritable bowel syndrome (IBS) is a functional bowel disorder, in which recurrent abdominal pain is associated with defecation or a change in bowel habits. STW 5-II is a combination of six medicinal herbs with a clinically proven efficacy in managing IBS. - Aim - This study aims to establish an in vitro IBS model using mouse intestinal organoids and to explore the anti-inflammatory and tight junction protective activities of the multi-herbal preparation STW 5-II. - Methods - Intestinal organoids were cultured in 1:1 Matrigel™ and medium domes. Inflammation and tight junction disruption were induced by a cocktail of cytokines (TNFα, IFNγ, IL-1β, IL-6) and bacterial proteins (LPS, flagellin). Organoids were treated with different concentrations of STW 5-II, and its multi-target activity was assessed using microarray analyses, RT-qPCR, immunofluorescence, western blot, immunohistochemistry, and a FITC permeability assay. In addition, we analyzed the expression of pNF-κB, pSTAT1, iNOS and ZO-1. In silico analyses were conducted to predict and identify the active components that may be responsible in mediating the multi-target anti-inflammatory activity of STW 5-II. - Results - An organoid based IBS model was successfully established. STW 5-II effectively reduced the cytokines-induced overexpression of the pro-inflammatory mediators pNF-κB, pSTAT1 and iNOS. Moreover, STW 5-II attenuated cytokine-mediated downregulation of the tight junction protein, ZO-1. This finding was confirmed by a FITC permeability assay. In silico analyses revealed a promising inhibitory activity of some isolated compounds from STW 5-II against NF-κB, STAT1 and iNOS. - Conclusion - STW 5-II possesses multiple anti-inflammatory as well as tight junction protective activities that could explain its clinically proven efficacy in managing IBS symptoms. 
650 4 |a Intestinal inflammation 
650 4 |a Irritable bowel syndrome 
650 4 |a Mouse intestinal organoids 
650 4 |a Proinflammatory cytokines 
650 4 |a Tight junctions 
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