Shengjiang Xiexin Decoction ameliorates DSS-induced ulcerative colitis via activating Wnt/β-Catenin signaling to enhance epithelium renovation and modulating intestinal flora

IF 8.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2025-04-01 Epub Date: 2025-02-01 DOI:10.1016/j.phymed.2025.156456
Chen Chen , Xiao-he Lin , Yi-min Xie , Shi-lin Xiong , Shao-zhen Hou , Song Huang , Hong-liang Jian , Yi-fan Wen , Xiao-yan Jiang , Jian Liang
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Abstract

Background

Shengjiang Xiexin Decoction (SJXXD) is a recognized formulation in traditional Chinese medicine that is commonly employed in diarrhea treatment. It has the potential to be a viable alternative for treating ulcerative colitis (UC), but its therapeutic effects and mechanisms remain unclear.

Purpose

This study aims to explore the effects and underlying mechanism of SJXXD in a mouse model of UC induced by dextran sulfate sodium (DSS).

Method

The components of SJXXD were analyzed using HPLC-Q/TOF-MS. UC mice model was established by freely drinking of 3% DSS, and SJXXD was administered as an intervention. After 7 days, body weight change, diarrhea, blood stools, colon length, cytokine levels, and key barrier proteins were evaluated to assess the therapeutic effect of SJXXD on UC. Additionally, transcriptome sequencing, quantitative polymerase chain reaction (qPCR), western blotting, intestinal organoids, 16S rRNA sequencing, and heat correlation analysis were employed to investigate the potential mechanisms of SJXXD on treating UC.

Results

SJXXD significantly inhibited weight loss, reduce diarrhea and bloody stools, lower disease activity index (DAI) score, suppressed inflammatory cell infiltration and cytokines secretion in colonic tissues in UC mice. Additionally, SJXXD also enhances the expression of tight junction and mucins. Transcriptome sequencing results indicate that SJXXD primarily activates the Wnt/β-Catenin pathway, thereby enhancing the expression of genes linked to intestinal stem cells and intestinal regeneration markers. At phylum level, SJXXD significantly increases the relative abundance of Verrucomicrobiota, while inhibiting Campylobacterota and Fusobacteriota. Importantly, the relative abundance of these bacterial phyla is significantly correlated with UC and Wnt/β-Catenin signaling pathway.

Conclusion

These results indicate that SJXXD can significantly treat DSS-induced mouse UC model by activating the Wnt/β-Catenin pathway and modulating intestinal flora. SJXXD may serve as a promising therapeutic approach for the management of UC.
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升江泻心汤通过激活Wnt/β-Catenin信号通路,促进上皮修复,调节肠道菌群,改善dss诱导的溃疡性结肠炎
生姜泻心汤(SJXXD)是一种公认的治疗腹泻的中药配方。它有可能成为治疗溃疡性结肠炎(UC)的可行选择,但其治疗效果和机制尚不清楚。目的探讨SJXXD在葡聚糖硫酸钠(DSS)致UC小鼠模型中的作用及其机制。方法采用HPLC-Q/TOF-MS对SJXXD的成分进行分析。采用3% DSS自由灌胃法建立UC小鼠模型,并给予SJXXD干预。7 d后观察体重变化、腹泻、血便、结肠长度、细胞因子水平和关键屏障蛋白水平,评价SJXXD对UC的治疗效果。此外,通过转录组测序、定量聚合酶链反应(qPCR)、western blotting、肠道类器官、16S rRNA测序和热相关分析,探讨SJXXD治疗UC的可能机制。结果jxxd显著抑制UC小鼠体重减轻,减少腹泻和血便,降低疾病活动指数(DAI)评分,抑制UC小鼠结肠组织炎症细胞浸润和细胞因子分泌。此外,SJXXD还增强了紧密连接蛋白和粘蛋白的表达。转录组测序结果表明,SJXXD主要激活Wnt/β-Catenin通路,从而增强肠道干细胞和肠道再生标志物相关基因的表达。在门水平上,SJXXD显著增加了Verrucomicrobiota的相对丰度,同时抑制弯曲杆菌和梭杆菌。重要的是,这些细菌门的相对丰度与UC和Wnt/β-Catenin信号通路显著相关。结论SJXXD通过激活Wnt/β-Catenin通路,调节肠道菌群,对dss诱导的小鼠UC模型有显著治疗作用。SJXXD可能是治疗UC的一种很有前途的治疗方法。
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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