STW 5 Herbal Preparation Modulates Wnt3a and Claudin 1 Gene Expression in Zebrafish IBS-like Model.

Autor: Piccione M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy., Facchinello N; Department of Biology, University of Padova, 35131 Padova, Italy., Schrenk S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy., Gasparella M; Department of Pediatric Surgery, Ca' Foncello Hospital, 31100 Treviso, Italy., Pathak S; Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India., Ammar RM; BAYER Consumer Health, Global Medical Affairs, 64295 Darmstadt, Germany.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafr-El Sheikh 33516, Egypt., Rabini S; BAYER Consumer Health, Global Medical Affairs, 64295 Darmstadt, Germany., Dalla Valle L; Department of Biology, University of Padova, 35131 Padova, Italy., Di Liddo R; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2021 Nov 28; Vol. 14 (12). Date of Electronic Publication: 2021 Nov 28.
DOI: 10.3390/ph14121234
Abstrakt: 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.
Databáze: MEDLINE
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