Clinical Analysis and Network Pharmacology in Revealing the Mechanism of Daifu Decoction on the Relapse of UC.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S497944

Yangyang Zhao, Danyang Cui, Yanan Xiao, Xu Han, Miao Jiang, Yang Gong

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Abstract

Background: Daifu Decoction (DFD), a patented herbal prescription used to prevent and treat ulcerative colitis (UC). This study aimed to reveal the effect of DFD on the relapse of UC and its mechanism via integrated retrospective clinical analysis, network pharmacology and in vivo and in vitro experimental validation.

Methods: First, the clinical data of UC patients treated with DFD were reviewed from a real-world study (RWS), and the relapse at 24 weeks after drug withdrawal was recorded to evaluate the relapse rate. Next, the chemical components of DFD were identified via ultra performance liquid chromatography‒mass spectrometry (UPLC‒MS), and the differentially expressed genes (DEGs) between UC patients in the active and remission stages were screened as disease targets related to the relapse of UC from the Gene Expression Omnibus (GEO) database. The core components, targets and key signalling pathways of DFD for preventing the relapse of UC were discussed via network pharmacology. Finally, the above results were verified via molecular docking and in vivo and in vitro experiments.

Results: A total of 475 UC patients were included, and the relapse rate of UC treated with DFD was 23.9%. Additionally, the 221 components identified by UPLC-MS and 398 DEGs related to the relapse of UC enriched the main pathway of the relapse of UC was IL-17 signaling pathway and the inflammatory-related targets, such as IL6, PTGS2, MMP7, MMP3, MMP1. Moreover, molecular docking revealed that the core components of DFD were able to bind to inflammation-related targets, and in vivo and in vitro experiments demonstrated that DFD could inhibit the IL-17 pathway, increase the level of claudin-1, and control inflammation to prevent UC relapse.

Conclusion: DFD can effectively prevent the relapse of UC which may be related to inhibiting the activation of IL-17 signalling pathway.

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大附汤治疗UC复发的临床分析及网络药理学研究。

背景：大附汤是一种用于预防和治疗溃疡性结肠炎（UC）的专利方剂。本研究旨在通过综合回顾性临床分析、网络药理学和体内外实验验证，揭示DFD对UC复发的影响及其机制。方法：首先，从真实世界研究（real-world study， RWS）中回顾使用DFD治疗UC患者的临床资料，记录停药后24周的复发率，评估复发率。接下来，通过超高效液相色谱-质谱法（UPLC-MS）鉴定DFD的化学成分，并从Gene Expression Omnibus （GEO）数据库中筛选活动期和缓解期UC患者之间的差异表达基因（DEGs）作为UC复发相关的疾病靶点。通过网络药理学探讨DFD预防UC复发的核心成分、靶点和关键信号通路。最后，通过分子对接和体内外实验对上述结果进行验证。结果：共纳入475例UC患者，DFD治疗UC复发率为23.9%。此外，UPLC-MS鉴定的221个组分和398个与UC复发相关的deg丰富了UC复发的主要途径是IL-17信号通路和炎症相关靶点，如IL6、PTGS2、MMP7、MMP3、MMP1。此外，分子对接发现，DFD的核心成分能够结合炎症相关靶点，体内和体外实验表明，DFD可以抑制IL-17通路，提高claudin-1水平，控制炎症，防止UC复发。结论：DFD可有效预防UC复发，其机制可能与抑制IL-17信号通路的激活有关。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.