基于生物信息学与系统药理学的斑蝥药理分子机制研究

Pharmacological Molecular Mechanism of Banmao(Mylabris) Based on Bioinformatics and System Pharmacology

目的:通过生物信息学和系统药理学方法、数据库和工具初步探讨斑蝥有效成分的药理作用的分子机制。方法:利用中药系统药理学分析平台(TCMSP)数据库获取斑蝥中有效成分及其有效成分的潜在靶标,并进一步获取这些靶标对应的疾病;运用网络可视化软件,构建斑蝥有效成分-靶点-疾病相互作用网络;借助DAVID工具进行斑蝥靶标群作用的生物学功能(GO分析)和信号通路的富集分析(KEGG分析),并运用OmicShare网络工具进行可视化;制作并分析斑蝥靶标的蛋白质相互作用(PPI)网络,将其GO分析结果可视化。结果:斑蝥主要相关疾病有癌症/肿瘤、炎症与感染、神经系统类、心血管类和代谢类;GO分析结果表明斑蝥主要通过类固醇激素介导的信号通路、腺苷酸环化酶调节G蛋白偶联受体信号通路、细胞增殖等作用发挥生物学功能;信号通路富集结果表明斑蝥主要作用蛋白与神经活性配体-受体相互作用、钙信号通路、PI3K-Akt信号通路等多途径发挥其药理作用;通过蛋白质相互作用,斑蝥靶标还可以影响来自RNA聚合酶Ⅱ启动子的转录起始、细胞内受体信号通路等生物学过程。结论:本研究结果与已有的斑蝥药理机制和应用是一致的,且更丰富。这能为进一步揭示和完善斑蝥的分子药理作用机制、开发新药和发现可能的新用法等提供指导。

Objective: To preliminarily explore the molecular mechanism of the pharmacological action of Banmao(mylabris) active ingredients by a series of bioinformatics and systematic pharmacological methods,databases and tools. Methods: Potential targets of active ingredients and their active ingredients in Banmao(mylabris) were obtained from TCMSP database, and diseases corresponding to these targets were further acquired.The effective ingredients-target-disease interaction network of Banmao(mylabris) was constructed by using network visualization software. The biological functions of target groups of Banmao(mylabris)(GO analysis) and disease interaction network were performed by DAVID tools. KEGG analysis of signaling pathways, and visualization using OmicShare network tools;production and analysis of cantharidin target protein interaction(PPI) network,and visualization of GO analysis results. Results: Text mining results showed that related diseases of Banmao(mylabris) include neoplastic diseases, inflammation/infection, cardiovascular diseases, neurological diseases and metabolic diseases. GO analysis indicated that Banmao(mylabris) played a biological role mainly through steroid hormone-mediated signaling pathways, adenylate cyclase-modulating G-protein coupled receptor signaling pathway, cell proliferation, and so on. The signaling pathway(KEGG) enrichment results showed that main active proteins of Banmao(mylabris) were related to the pathways of neuroactive ligand-receptor interaction, calcium signaling pathway, small cell lung cancer, PI3 K-Akt signaling pathway, and so on. And through the PPI, Banmao(mylabris) should also influence biological process of transcription initiation from RNA polymerase Ⅱ promoter, intracellular receptor signaling pathway, and so on. Conclusion: These results were accordance with the reported literature, and more sufficiently. These should be a guidance for further reveal the pharmacological molecular mechanism of Banmao(mylabris), new drug developing, and possibly new therapy.