基于网络药理学探讨青蒿琥酯治疗获得性免疫缺陷综合征的作用机制

Study on the mechanism of artesunate in the treatment of acquired immunodeficiency syndrome based on network pharmacology

目的通过网络药理学分析青蒿琥酯治疗获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)的靶点及信号通路探索其发挥作用的潜在机制。方法利用Pharmmapper及SwissTargetPrediction数据库检索青蒿琥酯相关的蛋白质靶点,检索GeneCards、OMIM、TTD及DRUGBANK数据库中AIDS的潜在靶点,应用韦恩图获取青蒿琥酯-AIDS交集靶点,通过String平台构建蛋白互作网络模型,应用Cytoscape中MCODE插件进行模块化分析,通过DAVID平台对其生物学过程及代谢通路进行富集分析。结果获取青蒿琥酯靶点333个,AIDS相关靶点1040个,青蒿琥酯治疗AIDS潜在作用靶点85个,通过String平台获得青蒿琥酯-AIDS靶点PPI网络共85个节点562条连接,筛选出雌雌激素受体1(estrogen receptor 1,ESR1)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、核受体亚家族3C组成员1(nuclear receptor subfamily 3 group C member 1,NR3C1)、胱天蛋白酶3(caspase 3,CASP3)、磷脂酰肌醇激酶-3催化亚单位α(phosphatidylinositol 3-kinase catalytic alpha polypeptide,PIK3CA)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、信号传导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)等核心基因。青蒿琥酯治疗AIDS设计的生物学过程主要包括信号传导、DNA复制、细胞增殖、血管生成、细胞迁移、血小板活化等,涉及的信号通路主要包括缺氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)、叉头盒转录因子O(forkhead box transcription tactor O,FoxO)、磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3/kinase-protein kinase B,PI3K/Akt)、大鼠肉瘤病毒(rat sarcoma virus,Ras)、Ras相关蛋白1(ras related protein 1,Rap1)及趋化因子信号通路等。结论本研究初步探索了青蒿琥酯治疗AIDS的靶点、信号通路及其相互作用关系,预测青蒿琥酯可通过不同生物学过程及信号通路发挥作用,为进一步开展青蒿琥酯治疗AIDS的临床及动物研究提供了一定的科学依据。

Objective: To analyze the target and signaling pathway and explore the potential mechanism of artesunate in the treatment of AIDS through network pharmacology. Methods: Artesunate related protein targets were retrieved from Pharmmapper and Swiss Target Prediction databases. Potential targets of AIDS were retrieved from Genecards, OMIM, TTD and Drugbank databases. The intersection target of artesunate and acquired immunodeficiency syndrome(AIDS) were obtained by Wayne diagram, the protein-protein interaction network model was constructed by string platform, and the MCODE plug-in in Cytoscape was used for modular analysis. The biological processes and metabolic pathways were analyzed by David platform. Results: 333 artesunate related targets and 1040 AIDS related targets were obtained. The artesunate-AIDS target PPI network has 85 nodes and 562 connections through the string platform. There were 85 potential targets of artesunate in the treatment of AIDS. Estrogen Receptor 1(ESR1), Mitogen-Activated Protein Kinase 1(MAPK1), Nuclear Receptor Subfamily 3 Group C Member 1(NR3 C1), Caspase 3(CASP3), Phosphatidylinositol 3-Kinase Catalytic Alpha Polypeptide(PIK3 CA), Epidermal Growth Factor Receptor(EGFR), Signal transducer and activator of transcription 3(STAT3) and other core genes were screened. The biological process of artesunate in the treatment of AIDS mainly includes signal transduction, DNA replication, cell proliferation, angiogenesis, cell migration, platelet activation and so on. The signal pathways involved mainly include Hypoxia-Inducible Factor-1(HIF-1), Forkhead Box Transcription Factor O(FoxO), Phosphatidylinositol 3/Kinase-Protein Kinase B(PI3 K/Akt), Rat Sarcoma Virus(Ras), Ras Related Protein 1(Rap1) and chemokine signaling pathways. Conclusion: This study preliminarily explored the target, signal pathway and its’ interaction of artesunate in the treatment of AIDS. This study predicted that artesunate could play a role through different biological processes and signal pathways. It provides a scientific basis for further clinical and animal research of artesunate in the treatment of AIDS.