Qi Yin San Liang San Decoction Relieves Gefitinib-Induced Diarrhea via the Modulation of Chemokines and Innate Immune Responses.

IF 2.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Current topics in medicinal chemistry Pub Date : 2025-06-13 DOI:10.2174/0115680266393963250611142026

Ke Yan, Qian Hua, Pengxiang Guo, Luyao Chen, Yufeng Chen, Haiyan Li, Xu Wang, Ya-Li Zhang, Yan Tan

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引用次数: 0

Abstract

Background: Gefitinib is associated with various adverse reactions, with diarrhea being prevalent. It is mainly managed through lifestyle changes and symptomatic pharmacological interventions, but these approaches have limited effectiveness and frequent recurrence. Qi Yin San Liang San Decoction (QYSLS) shows promise in relieving gefitinib-induced diarrhea, but its mechanisms are unclear.

Objective: This study aims to explore the pathological mechanisms underlying gefitinib-induced diarrhea and to elucidate the molecular pathways through which QYSLS mediates its therapeutic effects.

Methods: RNA-seq identified differentially expressed genes (DEGs) in colon samples from control and gefitinib-induced diarrhea rats. Network pharmacology was employed to predict the bioactive components and potential targets of QYSLS. A protein-protein interaction (PPI) network was utilized to explore the interactions among these targets, while GO, KEGG, and GSEA enrichment analyses were conducted to reveal the signaling pathways associated with these targets. RNA-seq was used to detect DEGs in QYSLS-mediated relieving of gefitinib-induced diarrhea; the intersection with potential targets was further analyzed to identify key genes. The expression of hub genes was validated through immunohistochemistry and RT-qPCR.

Results: RNA-seq and network pharmacology identified 103 bioactive components of QYSLS, with 84 potential targets in QYSLS relieving gefitinib-induced diarrhea. The DEGs in QYSLS relieving gefitinib-induced diarrhea and 84 potential targets were intersected, resulting in the identification of 26 key genes. Further analysis highlighted three central hub genes (CCL20, CCL25, NOS2), which were enriched in pathways related to innate immune response. Furthermore, immunohistochemistry and RT-qPCR confirmed that the expression of CCL25 was reduced by QYSLS in gefitinib-induced diarrhea rats.

Conclusion: These results indicate that QYSLS may exert its therapeutic effect on gefitinibinduced diarrhea via the modulation of chemokines and innate immune responses.

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气阴三良散汤通过调节趋化因子和先天免疫反应缓解吉非替尼所致腹泻。

背景：吉非替尼与各种不良反应相关，腹泻很普遍。主要通过改变生活方式和对症药物干预进行治疗，但这些方法效果有限且易复发。气阴三良散汤（QYSLS）对吉非替尼所致腹泻有一定的缓解作用，但其机制尚不清楚。目的：本研究旨在探讨吉非替尼致腹泻的病理机制，阐明QYSLS介导其治疗作用的分子途径。方法：采用RNA-seq技术对对照组和吉非替尼诱导腹泻大鼠结肠样本中的差异表达基因（DEGs）进行鉴定。采用网络药理学方法对其生物活性成分和潜在靶点进行预测。利用蛋白-蛋白相互作用（PPI）网络来探索这些靶点之间的相互作用，并通过GO、KEGG和GSEA富集分析来揭示与这些靶点相关的信号通路。采用RNA-seq检测qysls介导的吉非替尼腹泻缓解中的DEGs；进一步分析与潜在靶点的交集，以确定关键基因。通过免疫组织化学和RT-qPCR验证hub基因的表达。结果：RNA-seq和网络药理学鉴定出QYSLS的103个生物活性成分，其中84个是QYSLS缓解吉非替尼致腹泻的潜在靶点。将缓解吉非替尼腹泻的QYSLS中的DEGs与84个潜在靶点相交，鉴定出26个关键基因。进一步分析发现了三个中心枢纽基因（CCL20、CCL25、NOS2），它们在先天免疫应答相关通路中富集。此外，免疫组织化学和RT-qPCR证实，在吉非替尼诱导的腹泻大鼠中，QYSLS降低了CCL25的表达。结论：本实验结果提示清泻灵可能通过调节趋化因子和先天免疫应答来发挥其治疗吉非替尼腹泻的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current topics in medicinal chemistry 医学-医药化学

CiteScore

6.40

自引率

2.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.