网络药理学-分子对接技术探讨白药子抗肺癌的作用机制

Exploration of the mechanism of Baiyaozi against lung cancer by network pharmacology-molecular docking

目的基于网络药理学分析,筛查白药子化学成分及其抗肺癌的研究报道,阐释白药子生物碱成分治疗肺癌的可能作用机制。方法采用中药系统药理学数据库和分析平台(TCMSP)筛选合适的活性成分,使用Gene Cards数据库筛选抗肺癌相关靶点。利用PPI数据库构建白药子和肺癌交集的靶标,并通过Cytoscape软件构建“药物-靶点-疾病”的网络关系图,以活性成分为配体,用CB-Dock数据库进行分子对接。通过DAVID数据库对活性成分靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集和信号通路分析。结果白药子抗肺癌主要涉及6种活性化合物、88种潜在靶点、20种信号通路,分子对接结果表明,该活性物质具有良好的亲和力。其中以铵离子结合受体、神经递质受体等为主要候选靶点,以神经活性配体-受体相互作用、钙离子信号通路和多巴胺能神经突触进行网状综合调节为白药子抗肿瘤的主要调节机制。结论应用网络药理学分析,构成白药子抗肺癌“多种化合物、多种靶点和多种途径”的网络,为进一步阐明白药子治疗肺癌的作用机制奠定基础。

Objective Based on the network pharmacological analysis,to study the reports on the chemical constituents and anti-lung cancer effect of Baiyaozi(Radix Stephania cepharantha),and to explain the possible mechanism of the alkaloid components of Baiyaozi in the treatment of lung cancer.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database were used to screen active components,and Gene Cards database was used to screen anti-lung cancer related targets.The intersection target of Baiyaozi and lung cancer was constructed by PPI database,and the network diagram of"drug-target-disease"was constructed by Cytoscape software.The active components were used as ligands and CB-Dock database was used for molecular docking.The active component targets were enriched and analyzed by gene ontology(GO)and Jingdu gene and genome encyclopedia(KEGG)pathway through DAVID database.Results Baiyaozi′s anti-lung cancer mainly involved 6 kinds of active compounds,88 potential targets and 20 kinds of signal pathways.The results of molecular docking showed that the active substances have good affinity.Among them,ammonium binding receptors and neurotransmitter receptors are the main candidate targets,and the main anti-tumor mechanisms are neuroactive ligand-receptor interaction,calcium signal pathway and reticular comprehensive regulation of dopaminergic synapses.Conclusion With the application of network pharmacological analysis,Baiyaozi constitutes a network of"multiple compounds,multiple targets and multiple pathways"against lung cancer,which provides a basis for further elucidating the mechanism of Baiyaozi in the treatment of lung cancer.