目的 运用网络药理学和分子对接探讨澳洲茄边碱治疗鼻咽癌的潜在作用靶点以及可能存在的作用机制。方法 通过BATMAN、CTD、Genecards、HERB、Swiss Target Prediciton、TCMSP及Pharm Mapper数据库获取澳洲茄边碱潜在作用靶点，利用Drugbank、GeneCards、MalaCards、OMIM及OpenTarget数据库筛选鼻咽癌相关靶点，应用R语言软件筛选药物与疾病共同靶点，应用STRING_v12.0数据库、Cytoscape v3.10.0软件构建澳洲茄边碱–鼻咽癌共同靶点的蛋白相互作用（PPI）网络；基于R4.4.3软件用clusterProfiler包对澳洲茄边碱–鼻咽癌共同靶点进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析；最后，利用CytoNCA、MCODE插件及CytoHubba扩展程序计算节点得分，获得核心靶点，并通过AutoDockTools_1.5.7软件进行分子对接验证。结果 网络药理学分析得到澳洲茄边碱–鼻咽癌共同靶点121个，获得蛋白激酶B1（Akt1）、白蛋白（ALB）、膜联蛋白A5（ANXA5）、B细胞淋巴瘤2（Bcl2）、BCL2样1（Bcl2L1）、胱天蛋白酶-3（CASP3）、胱天蛋白酶-9（CASP9）、基质金属蛋白酶9（MMP9）、信号转导和转录激活因子3（STAT3）等29个核心靶点；GO显示澳洲茄边碱潜在靶点涉及最显著的生物过程（BP）为对脂多糖的反应和对细菌分子的反应，分子功能（MF）包括内肽酶活性、羧酸结合和蛋白丝氨酸/苏氨酸激酶活性，细胞组分（CC）是富纤维蛋白-1颗粒、细胞膜脂质筏和细胞膜微区等；KEGG通路分析涉及肿瘤坏死因子（TNF）信号通路、丝裂原激活的蛋白激酶（MAPK）信号通路、白细胞介素-17（IL-17）信号通路、p53信号通路等；分子对接结果显示，澳洲茄边碱与核心靶点均具有较好的结合能力。结论 澳洲茄边碱可能通过与Akt1、ALB等多靶点结合及调控TNF、MAPK等多信号通路来参与鼻咽癌免疫调控、细胞凋亡与存活，进而发挥抗鼻咽癌作用。

Objective To investigate the potential therapeutic targets and mechanisms of solamargine in the treatment of nasopharyngeal carcinoma based on network pharmacology and molecular docking. Methods Potential targets of solamargine were collected from BATMAN, CTD, GeneCards, HERB, SwissTargetPrediction, TCMSP, and PharmMapper databases. NPC-related targets were retrieved from DrugBank, GeneCards, MalaCards, OMIM, and OpenTarget databases. Common targets between solamargine and NPC were identified using R software. A protein-protein interaction (PPI) network was constructed with STRING_v12.0 database and Cytoscape v3.10.0. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using clusterProfiler packages in Rv4.4.3. Finally, core targets were identified by calculating node scores using the CytoNCA and MCODE plugins, along with the CytoHubba extension, followed by molecular docking validation performed with AutoDockTools_ 1.5.7 software. Results Common targets (121) of solamargine-nasopharyngeal carcinoma were obtained by network pharmacology analysis. There are 29 core targets such as Akt1, ALB, ANXA5, Bcl2, Bcl2L1, CASP3, CASP9, MMP9, STAT3 were identified. GO showed that the most significant BP involved in the potential targets of solamargine were response to lipopolysaccharide and response to molecule of bacterial origin, MF included endopeptidase activity, carboxylic acid binding and protein serine/threonine kinase activity, CC were ficolin-1-rich granule, membrane raft and membrane microdomain. KEGG pathway analysis involved TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and p53 signaling pathway, etc. The molecular docking results demonstrated that solamargine had the ability to bind to the core target. Conclusion Solamargine may participate in the immune regulation, apoptosis and survival of nasopharyngeal carcinoma by binding to multiple targets such as Akt1 and ALB and regulating multiple signaling pathways such as TNF and MAPK, thereby exerting an anti-nasopharyngeal carcinoma effect.

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北京医学奖励基金会课题研究项目（YXJL-2024-1324-0383）；广西药学会医院药学科研项目（GXYXH1-202206）