| 摘要: |
| 目的：通过网络药理学和分子对接技术研究葛花治疗急性酒精中毒的作用机制。方法：通过TCMSP数据库查询葛花的作用成分及靶点，采用Cytoscape软件制作“成分-靶点”网络，利用GeneCards、OMIM、DrugBank、DisGeNET收集急性酒精中毒相关的基因靶点。通过Venny 2.1.0获取成分和疾病的交集靶点基因，运用STRING构建蛋白质-蛋白质相互作用（PPI）网络，通过R软件进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析。采用分子对接技术验证核心化学成分和核心靶点的相互作用。结果：获得葛花活性成分18种，有效成分靶基因193个，排前10位的靶点是蛋白激酶B1（AKT1）、白细胞介素-6（IL-6）、p53蛋白（TP53）、白细胞介素-1β（IL-1β）、氨基末端激酶（JUN）、转化生长因子β1（TGFβ1）、基质金属蛋白酶-9（MMP9）、B细胞淋巴瘤2蛋白（BCL2）、半胱天冬酶-3（CASP3）、环氧化酶-2（PTGS2）。GO功能主要涉及对活性氧的反应、对脂多糖的反应、膜筏、膜微区、细胞因子受体结合、生长因子受体结合等。KEGG通路主要有流体剪切应力与动脉粥样硬化、脂质和动脉粥样硬化、非酒精性脂肪肝等。分子对接结合能<-5 kcal/mol，显示了良好的对接效果。结论：葛花通过IL-6、PTGS2、IL-1β等靶点来调控IL-17、Kelch样环氧氯丙烷相关蛋白1/核因子E2相关因子2（Keap 1/Nrf 2）等信号通路，发挥抑制细胞内氧化应激反应、减轻炎症反应等药理作用，从而达到治疗急性酒精性肝损伤的目的。 |
| 关键词: 急性酒精中毒 葛花 作用机制 网络药理学 分子对接技术 |
| DOI： |
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| Mechanism of action of Pueraria flower in treatment of acute alcoholism: A study based on network pharmacology and molecular docking |
| DENG Jiannan,CHEN Wenwen,ZHANG Feng |
| (Wuhan Hospital of Traditional Chinese Medicine，Wuhan 430010，Hubei，China) |
| Abstract: |
| Objective: To investigate the mechanism of action of Pueraria flower in the treatment of acute alcoholism based on network pharmacology and molecular docking.Methods: TCMSP database was used to obtain the active components of Pueraria flower and their targets，and Cytoscape was used to establish a component-target network.GeneCards，OMIM，DrugBank，and DisGeNET were used to collect the gene targets associated with acute alcoholism.Venny 2.1.0 was used to obtain the intersecting target genes between the active components and the disease，and STRING was used to establish a protein-protein interaction network.R software was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis.Molecular docking was used to validate the interaction between the core chemical components and the core targets.Results: A total of 18 active components were obtained for Pueraria flower，involving 193 target genes，among which the top 10 targets were AKT1，IL-6，TP53，IL-1β，JUN，TGF-βG，MMP9，BCL2，CASP3，and PTGS2.GO functions mainly involved response to reactive oxygen species，response to lipopolysaccharide，membrane raft，membrane microdomain，cytokine receptor binding，and growth factor receptor binding，and KEGG pathways mainly included fluid shear stress and atherosclerosis，lipid and atherosclerosis，and non-alcoholic fatty liver disease.Molecular docking obtained a binding energy of <-5 kcal/mol，suggesting a good binding effect.Conclusion: Pueraria flower exerts a therapeutic effect on acute alcoholism by regulating the signaling pathways such as IL-17 and Keap1/Nrf2，inhibiting intracellular oxidative stress response，and alleviating inflammatory response through the targets including IL-6，PTGS2，and IL-1β. |
| Key words: acute alcoholism Pueraria flower mechanism of action network pharmacology molecular docking |
