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临床分析与网络药理学揭示大腹汤治疗溃疡性结肠炎复发的机制

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

作者信息

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

机构信息

Department of Traditional Chinese Medicine, General Hospital of Northern Theater Command, Shenyang, Liaoning, People's Republic of China.

Institute of Basic Research in Clinical Medicine, China Academy of Traditional Chinese Medicine, Beijing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2025 Mar 7;19:1629-1653. doi: 10.2147/DDDT.S497944. eCollection 2025.

DOI:10.2147/DDDT.S497944
PMID:40070532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11895689/
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.

摘要

背景

代附汤(DFD)是一种用于预防和治疗溃疡性结肠炎(UC)的专利中药方剂。本研究旨在通过综合回顾性临床分析、网络药理学以及体内外实验验证,揭示代附汤对溃疡性结肠炎复发的影响及其作用机制。

方法

首先,从一项真实世界研究(RWS)中回顾接受代附汤治疗的UC患者的临床资料,并记录停药24周后的复发情况以评估复发率。其次,通过超高效液相色谱-质谱联用(UPLC-MS)鉴定代附汤的化学成分,并从基因表达综合数据库(GEO)中筛选活动期和缓解期UC患者之间的差异表达基因(DEGs)作为与UC复发相关的疾病靶点。通过网络药理学探讨代附汤预防UC复发的核心成分、靶点和关键信号通路。最后,通过分子对接以及体内外实验对上述结果进行验证。

结果

共纳入475例UC患者,代附汤治疗UC的复发率为23.9%。此外,通过UPLC-MS鉴定出的221种成分以及与UC复发相关的398个DEGs富集了UC复发的主要途径为IL-17信号通路以及炎症相关靶点,如IL6、PTGS2、MMP7、MMP3、MMP1。此外,分子对接显示代附汤的核心成分能够与炎症相关靶点结合,体内外实验表明代附汤可抑制IL-17通路,增加claudin-1水平,并控制炎症以预防UC复发。

结论

代附汤可有效预防UC复发,这可能与抑制IL-17信号通路的激活有关。

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