基于网络药理学探讨川楝子治疗急性髓细胞性白血病的作用靶点与机制

Exploring the therapeutic targets and mechanisms of Fructus Meliae Toosendan in acute myeloid leukemia based on network pharmacology

目的基于网络药理学及生物信息方法,分析川楝子治疗急性髓细胞性白血病(AML)的可能作用靶点与分子机制。方法通过TCMSP、Drugbank、Uniprot、SwissTargetPrediction等数据库分别获取川楝子与AML的相关靶点,经韦恩分析获取川楝子作用于AML的潜在靶点,并结合KEGG和GO分析,探讨川楝子发挥抗AML的作用机制;基于STRING数据库构建蛋白互作网络图,筛选其核心作用基因,采用分子对接技术分析小分子药物与疾病核心靶点的作用方式,并通过GEPIA数据库分析与患者预后密切相关的蛋白。结果网络药理学分析发现,川楝子可能通过作用于185个蛋白发挥抗AML的作用;GO分析和KEGG通路富集分析提示,川楝子通过影响细胞凋亡等生物过程,以及调控PI3K-Akt和MAPK等信号通路,影响AML的发生和发展;川楝子的有效成分与6个核心蛋白靶点均具有一定的结合活性,靶向作用于这些核心蛋白靶点可发挥抗AML的作用;GEPIA数据库分析发现人原癌基因酪氨酸蛋白激酶(proto-oncogene tyrosine-protein kinase Src,SRC)基因的表达与AML患者的预后密切相关,低表达SRC的患者预后较好,可能是川楝子抗AML的潜在作用靶点之一。结论川楝子中的有效成分可通过调控多靶点蛋白影响细胞凋亡,调控PI3K-Akt、MAPK信号分子等多种途径发挥抗AML的作用,SRC可能成为川楝子改善AML预后的潜在作用靶点之一。

Objective To analyze the potential therapeutic targets and molecular mechanisms of Fructus Meliae Toosendan(FMT)in the treatment of acute myeloid leukemia(AML),based on network pharmacology and bioinformatic approaches.Methods The relevant targets of FMT and AML were identified through TCMSP,DrugBank,Uniprot,SwissTargetPrediction and other databases,respectively,and the potential targets of FMT acting on AML were obtained by Venn analysis,which was combined with KEGG and GO analyses to explore the mechanisms of FMT exerting its anti-AML effects.A protein-protein interaction network was constructed based on the STRING database,identifying core functional genes.Molecular docking techniques were employed to analyze the interactions between small molecule drugs and core targets related to the disease.Additionally,the GEPIA database was utilized to investigate proteins closely associated with patient prognosis.Results Network pharmacology analysis revealed that FMT may exert its anti-AML effects by targeting 185 proteins.GO analysis and KEGG pathway enrichment indicated that FMT influences biological processes such as apoptosis and regulates signaling pathways like PI3K-Akt and MAPK,affecting the occurrence and progression of AML.The active components of FMT exhibited binding activity with six core protein targets,suggesting that targeting these proteins could play a role in anti-AML effects.Additionally,analysis from the GEPIA database showed that the expression of the proto-oncogene tyrosine-protein kinase Src(SRC)is closely related to the prognosis of AML patients,with low SRC expression correlating with better outcomes,indicating that SRC may be a potential target for the anti-AML effects of FMT.Conclusion The bioactive constituents of FMT may exert anti-AML effects through the regulation of multiple target proteins,the induction of apoptosis,and the modulation of signaling pathways,including PI3K-Akt and MAPK pathways.SRC could potentially serve as one of the targets through which FMT improves AML prognosis.