A network pharmacology approach to explore active compounds and pharmacological mechanisms of a patented Chinese herbal medicine in the treatment of endometriosis.
A network pharmacology approach to explore active compounds and pharmacological mechanisms of a patented Chinese herbal medicine in the treatment of endometriosis.
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从网络药理学角度探讨一种专利中药治疗子宫内膜异位症的活性成分及药理机制。
DOI：
10.1371/journal.pone.0263614
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Qu F
中科院分区：
文献类型：
--
作者：
Wu Y;Zhu Y;Xie N;Wang H;Wang F;Zhou J;Qu F
子宫内膜异位症是育龄妇女常见的良性疾病。曲氏方（QUF）是一种治疗子宫内膜异位症的专利中草药，已被证明可有效治疗和预防子宫内膜异位症复发。本研究旨在揭示其分子机制并探索潜在的药物靶点。通过中药系统药理学（TCMSP）和中药分子机制生物信息学分析工具（BATMAN-TCM）数据库和五个疾病基因数据库鉴定了QUF靶点和子宫内膜异位症相关基因集。进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析，并建立了蛋白质相互作用（PPI）网络以发现潜在机制。 MalaCards 搜索与子宫内膜异位症相关的靶点和信号通路，搜索结果也用于识别 QUF 的关键因素。进行分子对接以可视化有效分子与关键基因编码的蛋白质之间的相互作用。采用细胞实验和分子动力学（MD）模拟进一步验证QUF中活性化合物对子宫内膜异位症的治疗作用。生成了具有 117 个节点（94 个基因和 23 个活性化合物）和 224 个边的化合物目标网络。 GO和KEGG分析结果表明QUF可以通过调节免疫反应、细胞凋亡和增殖、氧化应激和血管生成来发挥作用。从 MalaCards 中相关性得分较高的两个关键子网络中选择 VEGFA、CXCL8、CCL2、IL1B 和 PTGS2 进行分子对接分析，QUF 的活性化合物对其具有结合潜力和高亲和力。槲皮素处理后CCL2、IL1B和PTGS2的mRNA表达水平显着降低。 MD模拟表明槲皮素和这些蛋白质的组合相对稳定。网络药理学策略整合了分子对接，以揭示QUF预防子宫内膜异位症的分子机制。我们的研究结果不仅证实了QUF的临床有效性，而且为进一步的实验研究提供了基础。
Endometriosis is a common benign disease in women of reproductive age. Qu’s formula (QUF) is a patented Chinese herbal medicine for treating endometriosis that has been proven to be effective in treating and preventing the recurrence of endometriosis. This study is aimed to discover its molecular mechanism and to explore the potential drug targets. A QUF target and endometriosis-related gene set was identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases and five disease-gene databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, and a protein–protein interaction (PPI) network was established to discover the potential mechanism. MalaCards was searched for targets and signaling pathways related to endometriosis, and the search results were also used to identify the key factors in QUF. Molecular docking was performed to visualize the interactions between the effective molecules and proteins encoded by critical genes. Cell experiments and molecular dynamics (MD) simulations were used to further validate the therapeutic effects of the active compounds in QUF on endometriosis. A compound-target network with 117 nodes (94 genes and 23 active compounds) and 224 edges was generated. The results of GO and KEGG analyses indicated that QUF could act by regulating the immune response, apoptosis and proliferation, oxidative stress, and angiogenesis. VEGFA, CXCL8, CCL2, IL1B and PTGS2 were selected for molecular docking analysis from two critical subnetworks with high correlation scores in MalaCards, and the active compounds of QUF had binding potential and high affinity for them. The mRNA expression levels of CCL2, IL1B and PTGS2 significantly decreased after treatment with quercetin. MD simulations showed that the combinations of quercetin and these proteins were relatively stable. The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism by which QUF protects against endometriosis. Our findings not only confirm the clinical effectiveness of QUF but also provide a foundation for further experimental study.
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DOI：
10.1093/database/bat018
发表时间：
2013
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Rappaport N;Nativ N;Stelzer G;Twik M;Guan-Golan Y;Stein TI;Bahir I;Belinky F;Morrey CP;Safran M;Lancet D
通讯作者：
Lancet D
影响因子：
6.7
作者：
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通讯作者：
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影响因子：
5.6
作者：
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通讯作者：
Esposito, Giuseppe
影响因子：
2.4
作者：
Zhang, Fan;Liu, Xiao-ling;Liu, Li-ping
通讯作者：
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影响因子：
81.5
作者：
Zondervan, Krina T.;Becker, Christian M.;Vigano, Paola
通讯作者：
Vigano, Paola