Piccione Monica, Facchinello Nicola, Schrenk Sandra, Gasparella Marco, Pathak Surajit, Ammar Ramy M, Rabini Sabine, Dalla Valle Luisa, Di Liddo Rosa
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Department of Biology, University of Padova, 35131 Padova, Italy.
Pharmaceuticals (Basel). 2021 Nov 28;14(12):1234. doi: 10.3390/ph14121234.
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.
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.
DSS treatment up-regulated the expression of , , , and 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 and in explanted zebrafish gut. Under inflammatory conditions, STW 5 downregulated the expression of the pro-inflammatory cytokine genes , , , and while it upregulated the expression of the anti-inflammatory genes and in enteric neuronal cells in vitro.
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.
肠易激综合征（IBS）是一种功能性肠病，其特征为慢性腹痛和大便异常。STW 5已被证明在包括IBS在内的功能性胃肠疾病中具有临床疗效，其作用途径是抑制炎症并保护黏膜。已知Wnt信号可调节NF-kβ依赖性炎性细胞因子的产生。这引发了在IBS样模型中评估STW 5对炎症反应和Wnt/β连环蛋白靶基因表达影响的想法。
我们使用斑马鱼和葡聚糖硫酸钠（DSS）处理在体内和体外模拟IBS样病症，并研究随后的STW 5处理对DSS处理的鱼以及原代培养的肠和神经细胞的肠道的影响。在处理的动物和/或细胞以及对照中分析肠道大体解剖结构、组织学以及Wnt信号和细胞因子基因的表达。
DSS处理上调了斑马鱼离体肠道中、、和的表达。随后的STW 5处理消除了肠道炎症的宏观体征、DSS诱导的黏液分泌表型，并使DSS诱导的斑马鱼离体肠道中il10和Wnt信号基因（如和）的上调表达恢复正常。在炎症条件下，STW 5下调了促炎细胞因子基因、、和的表达，同时上调了体外肠神经细胞中抗炎基因和的表达。
Wnt信号可能是STW 5抗炎和恢复肠道通透性作用的新靶点，这可能解释了其在IBS中的临床疗效。
