| 引用本文: | 乔雪,牟思霖,高尚,董妍伶,陈翰翰,李静蔚,陈宏志.基于网络药理学和分子对接探讨消瘿贴[]治疗桥本甲状腺炎的分子机制[J].生物信息学,2025,23(4):291-303. |
| QIAO Xue,MU Silin,GAO Shang,DONG Yanling,CHEN Hanhan,LI Jingwei,CHEN Hongzhi.Molecular mechanism of Xiaoying plaster in the treatment of Hashimotos thyroiditis based on network pharmacology and molecular docking[J].Chinese Journal of Bioinformatics,2025,23(4):291-303. |
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| 基于网络药理学和分子对接探讨消瘿贴[]治疗桥本甲状腺炎的分子机制 |
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乔雪1,2,牟思霖2,高尚3,董妍伶3,陈翰翰3,李静蔚3,陈宏志4
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(1.中国中医科学院 望京医院,北京 100102;2.山东中医药大学 第一临床医学院,济南 250014;3.山东中医药大学附属医院,济南 250014;4.山东中医药大学 中医学院,济南 250355)
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| 摘要: |
| 运用网络药理学和分子对接技术研究消瘿贴穴位贴敷治疗桥本甲状腺炎(HT)的潜在作用机制。在TCMSP中药系统药理学平台、HERB本草组鉴、BATMAN数据库和公开发表的文献中检索消瘿贴的主要成分和相应的蛋白质靶标。在GeneCards数据库收集HT的靶点,构建韦恩图获得复合靶标和疾病的交集靶点,并将靶标导入STRING数据库,使用Cytoscape 3.10.2软件构建蛋白质-蛋白质相互作用(PPI)网络。对交集靶点进行基因本体(GO)、京都基因与基因组百科全书(KEGG), Reactome, WikiPathways富集分析,以探索HT与消瘿贴的相关信号通路。对关键靶点和活性化合物进行分子对接研究。共获得消瘿贴的292种潜在活性化合物、3 434个疾病靶点与381个药物靶点,并得到261个交集靶点。通过PPI网络分析确定了10个关键靶点,Degree值排名前5位的靶点包括肿瘤蛋白P53(TP53)、蛋白激酶B1(AKT1)、转录因子AP-1(JUN)、肿瘤坏死因子(TNF)、原癌基因酪氨酸蛋白激酶(SRC)。GO、KEGG、Reactome和WikiPathways分析表明,消瘿贴治疗HT主要涉及RNA聚合酶II启动子的转录正调控、基因表达的正向调控、凋亡过程的负调控等生物学过程,信号通路主要包括白介素相关信号通路、PI3K/AKT、AGE-RAGE信号通路。分子对接结果表明,SRC与isorhamnetin具有较高的结合活性。槲皮素、芹菜素、β-谷甾醇、异鼠李素、甲氧基丁香酚是重要的活性化合物并通过分子对接模拟进行验证。本研究从多个角度阐明消瘿贴可能通过调节多个靶点和多条途径对HT起到治疗作用,可为进一步深入研究消瘿贴对HT的治疗作用提供科学依据。 |
| 关键词: 桥本甲状腺炎 穴位贴敷 网络药理学 分子对接 分子机制 |
| DOI：10.12113/202407003 |
| 分类号:R285 |
| 文献标识码:A |
| 基金项目:山东省中医药科技项目(No.M20241708);山东省医药卫生科技发展计划项目(No.202016001022; No.202204010433)；齐鲁医派中医学术流派传承项目(No.鲁卫函[2022]93号)；山东省中医药高层次人才培育项目(No.鲁卫函[2022]148号)；中华中医药学会春播行动中医药贴敷疗法项目(No.H20210908-04)；新锐肿瘤支持治疗课题研究项目(No.cphcf-2022-191). |
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| Molecular mechanism of Xiaoying plaster in the treatment of Hashimotos thyroiditis based on network pharmacology and molecular docking |
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QIAO Xue1,2, MU Silin2, GAO Shang3, DONG Yanling3, CHEN Hanhan3, LI Jingwei3, CHEN Hongzhi4
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(1. Wangjing Hospital,China Academy of Chinese Medical Sciences, Beijing 100102, China;2.The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China;3. Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China;4. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China)
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| Abstract: |
| To clarify the potential mechanism of Xiaoying plaster in the treatment of Hashimotos thyroiditis(HT) based on network pharmacology and molecular docking techniques. The main components and corresponding protein targets of Xiaoying plaster are searched in the TCMSP, HERB, BATMAN and papers. The targets of HT are collected from the GeneCards databases. A Venn diagram is constructed to obtain the intersection targets between the compound targets and disease targets, and the qualified targets are imported into the STRING database. The protein-protein interactions network is constructed using Cytoscape 3.10.2 Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), Reactome and WikiPathways enrichment analyses are performed on the intersection targets to explore the relevant signaling pathways of HT and Xiaoying plaster. Molecular docking studies.A total of 292 active components, 3 434 HT related targets, 381 interaction targets, and 261 intersection targets of Xiaoying plaster are collected. Through PPI network analysis, 10 key targets are identified, with the top five targets ranked by Degree values including tumor protein p53(TP53), protein kinase B1(AKT1), transcription factor AP-1(JUN), tumor necrosis factor(TNF), and sarcoma(SRC). GO, KEGG, Reactome and WikiPathways analyses indicated that Xiaoying plasters treatment of HT mainly involves biological processes such as positive regulation of transcription from RNA polymerase II promoter, positive regulation of gene expression, and negative regulation of apoptotic process. The signaling pathways mainly include the Signaling by Interleukins, PI3K-Akt, and AGE RAGE pathway. Molecular docking results show that SRC exhibited high binding activity with isorhamnetin. Quercetin, kaempferol, oleic acid, beta-elemene, eugenol, apigenin, and Methyleugenol are important active compounds and are verified through molecular docking simulations. This study clarifies from multiple perspectives that Xiaoying plaster may exert therapeutic effects on HT by regulating multiple targets and pathways, providing a scientific basis for further investigating the effects of Xiaoying plaster on HT. |
| Key words: Hashimotos thyroiditis Acupoint application Network pharmacology Molecular docking Molecular mechanisms |
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