Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2026-05-01 Epub Date: 2026-03-09 DOI:10.1016/j.molimm.2026.02.012

Jiawen Chen , Hui Peng , Jun Chen , Yi Liu , Lei Chen

{"title":"Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair","authors":"Jiawen Chen , Hui Peng , Jun Chen , Yi Liu , Lei Chen","doi":"10.1016/j.molimm.2026.02.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from \"clinical remission\" to \"mucosal healing\" and \"histological healing.\" This highlights the vital role of the interaction between intestinal stem cells (ISCs) and immune cells in maintaining and repairing intestinal tissue homeostasis. However, effective regulatory approaches targeting ISC-immune crosstalk are lacking in current clinical practice. The traditional Chinese medicine Qinjiao, which is widely used in clinical prescriptions for treating UC, contains many iridoid compounds, but whether they can promote tissue healing by regulating the ISC immune microenvironment remains to be clarified.</div></div><div><h3>Methods</h3><div>UHPLC-MS and an ISC injury organoid model were applied to identify and screen the four major iridoid compounds in Qinjiao. Then, the pharmacodynamic effects of swertiamarin (SW) on UC mice, the proliferation and differentiation of colonic ISCs, and the related status of Wnt, Notch, and Hippo-YAP signaling pathways were analyzed using RT-qPCR and other methods. Finally, the mechanism in organoids was verified using the YAP inhibitor Verteporfin.</div></div><div><h3>Results</h3><div>This study found that SW, a bioactive iridoid compound from Qinjiao, alleviated weight loss, mitigated colon atrophy, and reduced DAI scores in UC mice. SW also restored the proliferation and differentiation of ISCs. It mitigated immune-inflammatory responses and repaired the mucosal barrier by modulating YAP nuclear translocation to activate Wnt/β-catenin signaling and downregulate Notch signaling, enhancing ISC proliferation and differentiation.</div></div><div><h3>Conclusion</h3><div>This study revealed that iridoid compounds, represented by SW, are the primary active components in Qinjiao for treating UC by restoring mucosal barrier integrity through enhanced ISC proliferation and differentiation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 26-38"},"PeriodicalIF":3.7000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589026000441","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/3/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from "clinical remission" to "mucosal healing" and "histological healing." This highlights the vital role of the interaction between intestinal stem cells (ISCs) and immune cells in maintaining and repairing intestinal tissue homeostasis. However, effective regulatory approaches targeting ISC-immune crosstalk are lacking in current clinical practice. The traditional Chinese medicine Qinjiao, which is widely used in clinical prescriptions for treating UC, contains many iridoid compounds, but whether they can promote tissue healing by regulating the ISC immune microenvironment remains to be clarified.

Methods

UHPLC-MS and an ISC injury organoid model were applied to identify and screen the four major iridoid compounds in Qinjiao. Then, the pharmacodynamic effects of swertiamarin (SW) on UC mice, the proliferation and differentiation of colonic ISCs, and the related status of Wnt, Notch, and Hippo-YAP signaling pathways were analyzed using RT-qPCR and other methods. Finally, the mechanism in organoids was verified using the YAP inhibitor Verteporfin.

Results

This study found that SW, a bioactive iridoid compound from Qinjiao, alleviated weight loss, mitigated colon atrophy, and reduced DAI scores in UC mice. SW also restored the proliferation and differentiation of ISCs. It mitigated immune-inflammatory responses and repaired the mucosal barrier by modulating YAP nuclear translocation to activate Wnt/β-catenin signaling and downregulate Notch signaling, enhancing ISC proliferation and differentiation.

Conclusion

This study revealed that iridoid compounds, represented by SW, are the primary active components in Qinjiao for treating UC by restoring mucosal barrier integrity through enhanced ISC proliferation and differentiation.

Abstract Image

查看原文本刊更多论文

獐牙菜黄素通过调控yap介导的Wnt和Notch通路参与肠道干细胞修复治疗溃疡性结肠炎的机制研究

背景溃疡性结肠炎（UC）是一种慢性免疫介导的炎症性疾病。2024年，美国胃肠病学协会更新了UC患者的指南，将治疗目标从“临床缓解”转变为“粘膜愈合”和“组织学愈合”。这突出了肠道干细胞（ISCs）和免疫细胞之间的相互作用在维持和修复肠道组织稳态中的重要作用。然而，在目前的临床实践中，缺乏针对isc免疫串扰的有效调控方法。临床上广泛应用于UC治疗的中药沁娇含有多种环烯醚萜化合物，但其是否能通过调节ISC免疫微环境促进组织愈合尚不清楚。方法采用高效液相色谱-质谱法和ISC损伤类器官模型对秦角中4种主要环烯醚萜类化合物进行鉴定和筛选。然后，采用RT-qPCR等方法分析獐牙菜黄苷（SW）对UC小鼠的药理学作用、结肠ISCs的增殖和分化以及Wnt、Notch、hipo - yap信号通路的相关状态。最后，在类器官中使用YAP抑制剂维替波芬验证了其机制。结果本研究发现，来自秦角的生物活性环烯醚萜类化合物SW可减轻UC小鼠的体重减轻，减轻结肠萎缩，降低DAI评分。SW还能恢复ISCs的增殖和分化。它通过调节YAP核易位激活Wnt/β-catenin信号通路，下调Notch信号通路，促进ISC增殖分化，减轻免疫炎症反应，修复粘膜屏障。结论以SW为代表的环烯醚萜类化合物是秦角治疗UC的主要活性成分，其作用是通过增强ISC的增殖和分化来恢复粘膜屏障的完整性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.