PUBLICATION
STW 5 Herbal Preparation Modulates Wnt3a and Claudin 1 Gene Expression in Zebrafish IBS-like Model
- Authors
- Piccione, M., Facchinello, N., Schrenk, S., Gasparella, M., Pathak, S., Ammar, R.M., Rabini, S., Dalla Valle, L., Di Liddo, R.
- ID
- ZDB-PUB-211230-45
- Date
- 2021
- Source
- Pharmaceuticals (Basel, Switzerland) 14(12): (Journal)
- Registered Authors
- Dalla Valle, Luisa, Facchinello, Nicola
- Keywords
- IBS, NF-kβ, STW 5, Wnt signaling, claudin 1, wnt3a, zebrafish
- MeSH Terms
- none
- PubMed
- 34959635 Full text @ Pharmaceuticals (Basel)
Citation
Piccione, M., Facchinello, N., Schrenk, S., Gasparella, M., Pathak, S., Ammar, R.M., Rabini, S., Dalla Valle, L., Di Liddo, R. (2021) STW 5 Herbal Preparation Modulates Wnt3a and Claudin 1 Gene Expression in Zebrafish IBS-like Model. Pharmaceuticals (Basel, Switzerland). 14(12):.
Abstract
Aim Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal pain and stool irregularities. STW 5 has proven clinical efficacy in functional gastrointestinal disorders, including IBS, targeting pathways that suppress inflammation and protect the mucosa. Wnt signaling is known to modulate NF-kβ-dependent inflammatory cytokine production. This sparked the idea of evaluating the impact of STW 5 on the expression of inflammatory-response and Wnt/β catenin-target genes in an IBS-like model.
Main methods We used zebrafish and dextran sodium sulfate (DSS) treatment to model IBS-like conditions in vivo and in vitro and examined the effects of subsequent STW 5 treatment on the intestines of DSS-treated fish and primary cultured intestinal and neuronal cells. Gross gut anatomy, histology, and the expression of Wnt-signaling and cytokine genes were analyzed in treated animals and/or cells, and in controls.
Key findings DSS treatment up-regulated the expression of interleukin-8, tumor necrosis factor-α, wnt3a, and claudin-1 in explanted zebrafish gut. Subsequent STW 5 treatment abolished both the macroscopic signs of gut inflammation, DSS-induced mucosecretory phenotype, and normalized the DSS-induced upregulated expression of il10 and Wnt signaling genes, such as wnt3a and cldn1 in explanted zebrafish gut. Under inflammatory conditions, STW 5 downregulated the expression of the pro-inflammatory cytokine genes il1β, il6, il8, and tnfα while it upregulated the expression of the anti-inflammatory genes il10 and wnt3a in enteric neuronal cells in vitro.
Significance Wnt signaling could be a novel target for the anti-inflammatory and intestinal permeability-restoring effects of STW 5, possibly explaining its clinical efficacy in IBS.
Genes / Markers
Expression
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Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping