采用网络药理学方法结合实验验证，探讨fraxetin治疗急性髓系白血病（AML）的药理机制。通过Swisstarget预测、PhammerMap、CTDBASE等方法确定fraxetin的作用靶点。使用GeneCards和DisGenet数据库探索AML的疾病相关靶点，并在String网站中分析相交的靶点，构建蛋白质-蛋白质相互作用（PPI）网络。随后，利用DAVID数据库进行基因本体（GO）功能富集和京都基因与基因组百科全书（KEGG）通路富集。使用 Auto Dock Vina 软件进行核心蛋白与药物的分子对接。最后，通过体外实验评估了fraxetin对AML的作用。通过CCK8评估fraxetin对AML细胞增殖的影响，通过流式细胞术评估fraxetin对AML细胞凋亡的影响，并通过Western blotting检测相关蛋白靶点的表达来评估fraxetin的抗AML效果。在这项研究中，fraxetin 通过 101 个交叉基因发挥其抗 AML 的作用。通路富集分析表明，fraxetin对AML的药理作用与5'-单磷酸腺苷（AMP）激活蛋白激酶（AMPK）信号通路有关，分子对接结果表明，fraxetin对两者均具有良好的结合亲和力。核心目标和 AMPK。体外实验表明，fraxetin 可抑制 THP1 和 HL60 细胞的增殖并诱导其凋亡，并且 Western blotting 结果表明 fraxetin 干预组的 p-AMPK 发生剂量依赖性的显着变化。 Fraxetin 可能调节 AMPK通过与核心靶点相互作用来调节信号通路，从而对 AML 产生潜在的治疗作用。© 2024 作者。

To explore the pharmacological mechanism of the effect of fraxetin in treating acute myeloid leukemia (AML) by the network pharmacology method combined with experimental validation.The targets of fraxetin were identified through Swisstarget prediction, PhammerMap, and CTDBASE. Disease-related targets of AML were explored using GeneCards and DisGenet databases, and the intersected targets were analyzed in the String website to construct a protein-protein interaction (PPI) network. Subsequently, gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted using the DAVID database. Molecular docking of core proteins with drugs was performed using Auto Dock Vina software. Finally, the effect of fraxetin on AML was evaluated by in vitro experiments. The effect of fraxetin on AML cell proliferation was assessed by CCK8, the effect of fraxetin on AML cell apoptosis was assessed by flow cytometry, and the expression of relevant protein targets was detected by Western blotting to evaluate the anti-AML effect of fraxetin.In this study, fraxetin exerts its effect against AML through 101 intersecting genes. The pathway enrichment analysis revealed that the pharmacological effects of fraxetin on AML were related to the Adenosine 5'-monophosphate (AMP)-activated protein kinase （AMPK） signaling pathway, and the molecular docking results indicated that fraxetin had an excellent binding affinity to both the core target and AMPK. In vitro experiments have demonstrated that fraxetin inhibited the proliferation and induced apoptosis of THP1 and HL60 cells, and the western blotting results indicated that the p-AMPK of the fraxetin intervention group was significantly changed in a dose-dependent manner.Fraxetin may modulate the AMPK signal pathway by interactine with the core target, thereby potentially therapeutic effect on AML.© 2024 The Authors.