青娥丸治疗椎间盘退变机制的网络药理学及实验验证
Network Pharmacology and Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration.
作者信息
Jin Hui, Ma Huaiyu, Wu Jie, Wu Ruizhe, Xu Haoran, Chen Weixing, Li Linghui, Zeng Jingqi, Wang Fan
机构信息
Department of Orthopedics, the Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, China.
Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China.
出版信息
Curr Comput Aided Drug Des. 2025;21(4):534-548. doi: 10.2174/0115734099356426241119051916.
OBJECTIVE
The Qing'e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.
METHODS
Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.
RESULTS
We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.
CONCLUSION
The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.
目的
青娥丸（QEP）被广泛用于缓解由椎间盘退变（IDD）引起的腰痛和坐骨神经痛。然而，其活性成分、关键靶点和分子机制尚未完全明确。本研究旨在利用数据库挖掘技术阐明QEP改善IDD的分子机制。
方法
使用中药系统药理学数据库和分析平台以及中药分子机制生物信息学分析工具来确定QEP的活性成分和候选靶点。从GeneCards数据库中获取IDD相关靶点，并从BioGPS数据库中检索肝肾特异性基因。分析这些候选靶点的交集，以确定QEP在IDD中的潜在靶点。使用STRING和Cytoscape 3.7.2软件进行蛋白质-蛋白质相互作用网络分析。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析进一步分析核心靶点。采用分子对接评估活性成分与候选靶点的结合亲和力，并进行动物实验验证。
结果
我们确定了QEP的65种潜在活性成分，它们对应1093个候选靶点、2108个IDD相关靶点和1113个肝肾特异性基因。关键成分包括槲皮素、小檗碱、异鼠李素和大黄素。主要候选靶点为Wnt5A、CTNNB1、IL-1β、MAPK14、MMP9和MMP3。GO和KEGG分析表明这些靶点参与Wnt信号传导、TNF信号传导、Wnt受体激活、卷曲蛋白结合和Wnt-蛋白质相互作用。分子对接显示这些成分与其靶点之间有强烈的结合。动物实验表明，与模型组相比，高、中、低剂量的QEP治疗均显著降低了Wnt5A、CTNNB1、IL-1β、MAPK14、MMP9和MMP3的表达。
结论
QEP通过调节Wnt/MAPK/MMP信号通路并减少关键因子的释放和激活来缓解IDD。
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