基于网络药理学及分子对接技术分析西黄丸治疗食管癌作用机制
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R285.5

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吉林省中医药科技项目(2023015)


Analysis of Mechanism of Action of Xihuang Pills in the Treatment of Esophageal Cancer Based on Network Pharmacology and Molecular Docking Techonolgy
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    摘要:

    目的:采用网络药理学及分子对接技术分析西黄丸治疗食管癌的潜在作用机制。方法:应用中药 系统药理学数据库与分析平台(TCMSP) 及相关文献获取西黄丸的活性成分及对应的作用靶点,使用R 4.4.1 软件进行筛选合并,借助GeneCards、OMIM、pharmGKB、CTD、TTD等数据库得到食管癌的疾病靶点,将药 物疾病靶点取交集;利用Cytoscape3.10.3软件构建中药复方调控网络图和蛋白质互作(PPI) 网络图;基于 David数据库进行基因本体(GO) 功能和京都基因与基因组百科全书(KEGG) 通路富集分析,并对核心成分 和靶点进行分子对接验证。结果:共筛选出57个有效成分,400个药物靶点,7 330个疾病靶点,307个交集靶 点。根据中药复方调控网络和PPI网络的拓扑分析结果,筛选出肿瘤蛋白P53(TP53)、AKT丝氨酸/苏氨酸蛋 白激酶1(AKT1)、酪氨酸蛋白激酶(SRC)、表皮生长因子受体(EGFR) 等关键靶点,槲皮素、乙酰基-11- 酮基-β-乳香酸(AKBA)、乳香酸等核心成分。获取GO条目627个,主要涉及炎症、凋亡等方面。KEGG通路 113条,主要涉及癌症通路、炎症与免疫、增殖与凋亡、氧化应激等信号通路。分子对接显示核心靶点与关键 成分具有良好的结合力。结论:西黄丸可能通过槲皮素、AKBA、乳香酸等有效成分,调控大鼠肉瘤病 毒(Ras)、磷脂酰肌醇3 激酶/蛋白激酶B (PI3K/Akt)、腺苷酸活化蛋白激酶/去乙酰化酶1/叉头框蛋 白(AMPK/SIRT1/FOXO) 等信号通路发挥治疗食管癌的作用。

    Abstract:

    Abstract: Objective: To analyze the potential mechanism of Xihuang Pills in the treatment of esophageal cancer (EC) using network pharmacology and molecular docking validation. Methods: The active ingredients of Xihuang Pills and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant literature. R 4.4.1 software was used for screening and integration. Disease targets for EC were obtained from databases including The Human Gene Database (GeneCards), On-line Mendelian Inheritance in Man (OMIM) , Pharmacogenetics and Pharmacogenomics Knowledge Base (pharmGKB), Comparative Toxicogenomics Database (CTD), and Therapeutic Target Database (TTD). The intersection between drug and disease targets was taken. Cytoscape 3.10.3 software was employed to construct a Chinese medicine compound regulation network and a protein-protein interaction (PPI) network. Gene Ontology( GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Molecular docking validation was conducted for core ingredients and targets. Results:A total of 57 active ingredients,400 drug targets,7 330 disease targets, and 307 intersection targets were screened. Based on the topological analysis of the Chinese medicine compound regulation network and PPI network,key targets such as tumor protein P53 (TP53),AKT serine/threonine kinase 1 (AKT1), tyrosine-protein kinase SRC (SRC), and epidermal growth factor receptor (EGFR), as well as core ingredients including quercetin, acetyl-11-keto- β -boswellic acid (AKBA), and boswellic acid, were identified. Analysis yielded 627 GO terms, primarily related to inflammation and apoptosis. In total, 113 KEGG pathways were identified,mainly involving cancer pathways,inflammation and immunity,proliferation and apoptosis, oxidative stress,and other signaling pathways. Molecular docking showed that the core targets and key ingredients had strong binding affinity. Conclusion:Xihuang Pills may exert therapeutic effects on EC through active ingredients like quercetin, AKBA, and boswellic acid by regulating signaling pathways such as rat sarcoma (Ras) virus, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt),and AMP-activated protein kinase/sirtuin 1/forkhead box protein O( AMPK/SIRT1/FOXO)

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侯怡君,王汉,隋晓丹,王誉睿,孙艳婷,周丽雅.基于网络药理学及分子对接技术分析西黄丸治疗食管癌作用机制[J].新中医,2025,57(23):197-207

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  • 在线发布日期: 2025-12-12
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