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基于蒲公英-桑叶治疗急性髓系白血病潜在机制的网络药理学分析
周鑫辰,董姝含,张卓,沈明妹,汪香君,李迎,刘丽梅
PDF(3559 KB)
PDF(3559 KB)
基于蒲公英-桑叶治疗急性髓系白血病潜在机制的网络药理学分析
Network pharmacology analysis based on potential mechanism of dandelion-mulberry leaf in treatment of acute myeloid leukemia
目的 应用网络药理学分析蒲公英-桑叶在急性髓系白血病(AML)发生发展过程的作用,阐明其治疗 AML 的活性成分和作用机制。 方法 通过中药系统药理数据库和分析平台(TCMSP)筛选蒲公英-桑叶的活性成分,采用SwissTargetPrediction数据库预测其作用靶点,在症状映射(SymMap)数据库、人类基因数据库(GeneCards)、DisGeNET数据库和在线人类孟德尔遗传(OMIM)数据库中检索AML相关基因和蛋白靶点。对AML相关基因和蒲公英-桑叶靶基因进行比较,确定富集基因,并进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)信号通路富集分析。采用Cytoscape 3.8.0软件根据靶点信息构建药物-有效成分-靶点网络和蛋白-蛋白互作(PPI)网络,采用CytoNCA插件筛选出核心基因,通过AutoDock软件进行分子对接验证。 结果 对数据库检索结果进行筛选后得到39种有效成分,收集蒲公英-桑叶与AML的共同靶点148个。GO功能富集分析主要涉及细胞因子介导的信号传导途径、激酶活性正向调节和氧化应激反应等。KEGG信号通路富集分析主要涉及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路、肿瘤坏死因子(TNF)信号通路和Janus激酶/信号转导和转录激活因子(JAK/STAT)信号通路等。拓扑分析得到信号转导和转录激活因子3(STAT3)、表皮生长因子受体(EGFR)、蛋白激酶B1(AKT1)、重组人表皮生长因子(EGF)、血管内皮生长因子A(VEGFA)、原癌基因MYC、肿瘤蛋白P53(TP53)、丝裂原活化蛋白激酶3(MAPK3)、含半胱氨酸的天冬氨酸蛋白水解酶3(CASP3)、肉瘤基因SRC、热休克蛋白90α家族A类成员1(HSP90AA1)、连环蛋白B1(CTNNB1)、磷酸肌醇3-激酶催化亚基α(PIK3CA)、白细胞介素6(IL-6)、TNF、丝裂原活化蛋白激酶1(MAPK1)和磷酸肌醇3-激酶调节亚基1(PIK3R1)等核心靶点。分子对接,结合亲和力最高的配对结果为蒲公英萜醇(taraxerol)与MYC(-8.74 kcal·mol-1),槲皮素(quercetin)、kaemfprol、木犀草素(luteolin)和artemetin与各个靶点均有很好的结合亲和力。 结论 蒲公英-桑叶主要活性成分quercetin、taraxerol、kaemfprol、luteolin和artemetin可能通过调控AKT1、STAT3、HSP90AA1、IL-6和MAPK1发挥抗AML的作用,对PI3K-AKT信号通路的调节是蒲公英-桑叶发挥抗AML作用的重要机制。
Objective To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia (AML) by network pharmacology, and to clarify the active components and their mechanisms in treating AML. Methods The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets were predicted by SwissTargetPrediction Database. The AML-related genes and protein targets were retrieved from the SymMap Database, the GeneCards Human Gene Database, the DisGeNET Database, and the Online Mendelian Inheritance in Man (OMIM) Database. The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. The drug-active component-target network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.8.0 software, and the core genes were selected by CytoNCA plugin; the molecular docking was conducted by AutoDock software. Results After filtering by databases, 39 active components were identified, and 148 common targets between dandelion-mulberry leaf and AML were collected. The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways, positive regulation of kinase activity, and oxidative stress responses. The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) signaling pathway, the tumor necrosis factor (TNF) signaling pathway, and the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. The key targets were identified by topological analysis including signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), protein kinase B1 (AKT1), recombinant human epidermal growth factor (EGF), vascular endothelial growth factor A (VEGFA), oncogene MYC, tumor protein P53 (TP53), mitogen-activated protein kinase 3 (MAPK3), cysteiny asparate specific protease-3 (CASP3), oncogene SRC, heat shock protein 90 alpha family class A member 1 (HSP90AA1), tenascin XB1 (CTNNB1), phosphoinositide kinase-3 catalytic subunit alpha (PIK3CA), interleukin 6 (IL-6), TNF, mitogen-activated protein kinase 1(MAPK1), and phosphatidylinositide kinase-3 regulatory subunit 1 (PIK3R1). The molecular docking results showed the highest affinity pairing to be taraxerol with MYC (-8.74 kcal·mol-1), and quercetin, kaempferol, luteolin, and artemetin demonstrated good binding affinities with various targets. Conclusion The main active components of dandelion-mulberry leaf, such as quercetin, taraxerol, kaempferol, luteolin, and artemetin, may exert the anti-AML effect by regulating AKT1, STAT3, HSP90AA1, IL-6, and MAPK1; regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.
急性髓系白血病 / 蒲公英 / 桑叶 / 网络药理学 / 分子对接
Acute myeloid leukemia / Dandelion / Mulberry leaf / Network pharmacology / Molecular docking
R733.7
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