基于网络药理学、分子对接及分子动力学模拟探讨甘草查尔酮A治疗阿尔茨海默病的作用机制研究

目的 从分子层面探讨甘草查尔酮A治疗阿尔茨海默病（AD）的作用机制。方法 通过TCMSP、PharmMapper、SwissTargetPrediction、CTD及DisGeNET等数据库检索出甘草查尔酮A的作用靶点及其与AD相关的靶点的交集。利用Cytoscape 3.7.2软件的ClueGO功能对交集蛋白作KEGG通路富集分析。最终通过分子对接及分子动力学模拟方法从分子层面研究甘草查尔酮A作用于AD相关靶点的结合位点及结合能力。结果 甘草查尔酮A的作用靶点有128个，其中与AD相关的靶点112个，这些靶点涉及信号通路33条，包括MicroRNAs in cancer、Serotonergic synapse及Cell cycle等，从而构建出靶蛋白蛋白相互作用（PPI）、单一成分-靶点-生物学通路网络。分子对接及分子动力学模拟结果显示，甘草查尔酮A与PPI网络图中度值最高的20个靶蛋白均能很好地结合，其中结合性最好的3个靶蛋白分别为视网膜母细胞瘤相关蛋白、环氧合酶2和丁酰胆碱酯酶。结论 从分子层面对甘草查尔酮A治疗AD作用机制进行初步探讨，揭示潜在的生物学机制，为其应用提供理论依据。

Mechanism of licochalcone A in treatment of Alzheimer's disease on network pharmacology, molecular docking, and molecular dynamics simulation

Objective To explore the molecular mechanism of licochalcone A in the treatment of Alzheimer''s disease. Methods A network pharmacology approach comprising compound target prediction, Alzheimer''s disease genes collection, and network analysis has been used to explore the pharmacological mechanism of licochalcone A in the treatment of Alzheimer''s disease. And the molecular docking and molecular dynamics simulation approaches were used to explore its molecular mechanism. Results A total of 128 potential drug targets were obtained according to the screening, 112 of which are related to Alzheimer''s disease, such as Butyrylcholinesterase, Cyclooxygenase-2, Retinoblastoma-associated protein and so on. The results of molecular docking and molecular dynamics simulation revealed the binding mode of licochalcone A molecule with these proteins. Licochalcone A exerts its effects on Alzheimer''s disease mainly by acting on 33 signal pathways, such as MicroRNAs in cancer, Serotonergic synapse, Cell cycle and so on. Conclusion The present investigation showing the pharmacological mechanism of licochalcone A in the treatment of Alzheimer''s disease at the molecular level, lay a certain theoretical foundation of licorice chalcone A in the future.