基于网络药理学和分子对接技术对三物黄芩汤治疗肝癌的机制分析及实验观察  

A Network Pharmacology-and Molecular Docking-Based Analysis of the Anti-Hepatoma Mechanisms of Sanwu Huangqin Decoction with Experimental Validation

作　　者：王华真 何磊 孟祥宇 谢圆魁 WANG Huazhen;HE Lei;MENG Xiangyu;XIE Yuankui(The Second People's Hospital of Zhumadian,Zhumadian 463000,China)

机构地区：[1]驻马店市第二人民医院,驻马店463000

出　　处：《世界科学技术-中医药现代化》2024年第3期819-828,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：驻马店市第二人民医院院内项目(2021-ZMDSPH-002):重症抑郁障碍患者认知障碍的炎症代谢机制及相关健康危险因素的研究,负责人:何磊。

摘　　要：目的通过网络药理学和分子对接技术分析三物黄芩汤治疗肝癌的潜在作用机制,并通过动物实验进行初步验证。方法运用TCMSP数据库筛选三物黄芩汤的有效化合物,运用Drug bank、Pharm mapper、Uniport、PubMed等数据库获得三物黄芩汤的作用靶点,运用Gene cards和TCGA数据库获得肝细胞癌相关靶点,与上述三物黄芩汤作用靶点取交集后得到“药物-疾病”靶点,运用String数据库构建蛋白相互作用网络,运用David和KEGG数据库进行GO、KEGG富集分析,运用Cytoscape软件构建相应网络。运用Discovery studios软件进行分子对接,对上述网络药理学结果进行验证。采用C57小鼠肝脏原位荷瘤模型,观察三物黄芩汤干预对肝癌细胞增殖、转移的影响,并观察肝癌细胞IL-6分子表达的变化。结果三物黄芩汤有效成分81个,核心成分10个,作用靶点249个,肝癌样本与正常样本差异靶点1420个,两者交集59个。蛋白相互作用网络频数分析显示,三物黄芩汤治疗肝细胞癌的机制与ESR1、MYC、JUN、IL-6、MMP9、EGF等靶点有关。GO和KEGG富集分析表明以IL-6为核心的IL-17 signaling pathway、TNF signaling pathway、Toll-like receptor signaling pathway等多条信号通路可能发挥重要作用。分子对接结果显示,药效分子Acacetin、Wogonin、Baicalein、Oroxylina、Beta-sitosterol、8-Isopentenylkaempferol、Formononetin、Luteolin、Quercetin、Stigmasterol可与IL-6蛋白结合,进一步证实了上述结果。动物实验表明,三物黄芩汤可抑制肝种植瘤的大小和肺部转移,癌细胞IL-6含量降低,初步验证了三物黄芩汤的抗肝癌作用和机制。结论本研究通过网络药理学和分子对接技术发现IL-6是三物黄芩汤治疗肝癌的关键靶点,进一步通过动物实验表明三物黄芩汤可降低肝癌组织IL-6表达量发挥治疗肝癌作用,为三物黄芩汤的抗肝癌应用提供理论依据。Objective Exploring the mechanisms of Sanwu Huangqin Decoction in the treatment of liver tumors based on network pharmacology and molecular docking technologies and experimental observations.Methods TCMSP database was used to screen the effective compounds contained in Sanwu Huangqin decoction,Drug bank,Pharm mapper,Uniport,PubMed and other databases were used to obtain the action targets of Sanwu Huangqin decoction,gene cards and TCGA databases were used to obtain the related targets of hepatocellular carcinoma,and the"drug-disease"target genes were obtained after the intersection with the action targets of Sanwu Huangqin decoction,and the protein interaction network was constructed using string database,David and KEGG databases were used for go and KEGG enrichment analysis,Cytoscape software was used to build the corresponding network,and discovery studios software was used for molecular docking to verify the above network pharmacology related results.The effects of Sanwu Huangqin decoction on the proliferation,the metastasis and the expression of IL-6 of cancer cells were observed.Results 81effective components and 10 key components of Sanwu Huangqin decoction,249 targets,1420 differential targets between tumor samples and normal samples were obtained,and 59 overlapping targets were obtained.Frequency analysis of protein interaction network:the potential mechanism of Sanwu Huangqin Decoction in treating hepatocellular carcinoma is related to ESR1,Myc,Jun,IL-6,MMP9,EGF,etc.Through GO and KEGG enrichment analysis,IL-17signaling pathway,TNF signaling pathway,Toll like receptor signaling pathway may play important roles.The results of molecular docking showed that acacetin,wogonin,baicalein,oroxylin a,beta sitosterol,8-isoopenenyl-kaempferol,formononetin,luteolin,quercetin,and stigmastrol bound to IL-6 protein,which further confirmed the above results.Animal experiments showed that Sanwu Huangqin decoction could inhibit the tumor size and the pulmonary metastasis,and the content of IL-6 in cancer cells was decreas

关 键 词：三物黄芩汤 肝癌 网络药理学 分子对接 IL-6 

分 类 号：R285[医药卫生—中药学]