基于网络药理学和分子对接技术探索山豆根抗鼻咽癌的作用机制与物质基础

To Explore the Mechanism of Action and Material Basis of Sophora tonkinensis Gagnep in the Treatment of Nasopharyngeal Carcinoma Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：基于网络药理学和分子对接技术探索山豆根抗鼻咽癌(nasopharyngeal carcinoma, NPC)的作用机制与物质基础。方法：前期研究获取山豆根的活性成分。通过Swiss Target Prediction数据库筛选出山豆根化学成分的潜在作用靶点；GeneCards、OMIM、CTD等数据库检索鼻咽癌的潜在基因靶点；使用Venny 2.0.1平台筛选药物与疾病作用的交集靶点；将药物与疾病的交集靶点导入至String平台构建蛋白互作(PPI)网络，将PPI网络导入Cytoscape软件筛选核心靶点，在Cytoscape软件中制作“中药–活性成分–靶点–疾病”网络图筛选核心活性成分。应用DAVID数据库进行GO和KEGG富集分析，预测涉及的生物过程与代谢通路。使用CB-DOCK2对山豆根抗鼻咽癌的核心活性成分及核心靶点进行分子对接。结果：本研究共筛选山豆根抗鼻咽癌的31个有效活性成分以及51个交集靶点，其中核心活性成分主要包括葛根素、大豆苷、白蜡树素等；核心靶点主要包括MMP9、肿瘤坏死因子(TNF-α)、MMP1、MMP2、IL2等。GO分析主要涉及单碳代谢过程、兴奋性突触后电位、单原子离子跨膜转运等生物过程，KEGG分析主要富集在氮代谢信号通路、炎症性肠病信号通路、膀胱癌信号通路等信号通路。分子对接结果显示核心靶点与对应的活性成分具有良好的结合能力。结论：应用网络药理学和分子对接技术预测山豆根抗鼻咽癌的作用机制以及物质基础，为其进一步研究提供新的思路与线索。

Abstract: Objective: To explore the mechanism of action and material basis of Sophora tonkinensis Gagnep in the treatment of nasopharyngeal carcinoma based on network pharmacology and molecular docking technology. Method: Preliminary research was conducted to identify the active components of Sophora tonkinensis Gagnep. The Swiss Target Prediction database was utilized to screen for potential targets of the chemical constituents of Sophora tonkinensis Gagnep. GeneCards, OMIM, CTD, and other databases were searched to identify potential gene targets for nasopharyngeal carcinoma. The Venny 2.0.1 platform was employed to filter the intersection of drug and disease targets. The intersection targets were imported into the String platform to construct a protein-protein interaction (PPI) network, which was then imported into Cytoscape software to identify core targets and create a “Chinese medicine-active ingredient-targets-disease” network to filter core active ingredients. The DAVID database was applied for GO and KEGG enrichment analysis to predict the biological processes and metabolic pathways involved. CB-DOCK2 was used for molecular docking of the core active ingredients and core targets of Sophora tonkinensis Gagnep against nasopharyngeal carcinoma. Result: This study screened 31 effective active ingredients and 51 intersecting targets of Sophora tonkinensis Gagnep for anti nasopharyngeal carcinoma, among which the core active ingredients mainly include puerarin, daidzein, and dimethylfraxetin; The core targets mainly include MMP9, tumor necrosis factor alpha (TNF-α), MMP1, MMP2, IL2, etc. GO analysis mainly involves a single carbon metabolism process, excitatory postsynaptic potential, monoatomic ion transmembrane transport and other biological processes. KEGG analysis mainly concentrates on the nitrogen metabolism signal pathway, inflammatory bowel disease signal pathway, bladder cancer signal pathway and other signal pathways. The molecular docking results showed that the core target had good binding ability with the corresponding active ingredient. Conclusion: The application of network pharmacology and molecular docking technology to predict the mechanism of action and material basis of the anti nasopharyngeal carcinoma effect of Sophora tonkinensis Gagnep provides new ideas and clues for further research.