目的 從分子層面探討甘草查爾酮A治療阿爾茨海默病（AD）的作用機制。方法 通過TCMSP、PharmMapper、SwissTargetPrediction、CTD及DisGeNET等數(shù)據(jù)庫檢索出甘草查爾酮A的作用靶點及其與AD相關(guān)的靶點的交集。利用Cytoscape 3.7.2軟件的ClueGO功能對交集蛋白作KEGG通路富集分析。最終通過分子對接及分子動力學(xué)模擬方法從分子層面研究甘草查爾酮A作用于AD相關(guān)靶點的結(jié)合位點及結(jié)合能力。結(jié)果 甘草查爾酮A的作用靶點有128個，其中與AD相關(guān)的靶點112個，這些靶點涉及信號通路33條，包括MicroRNAs in cancer、Serotonergic synapse及Cell cycle等，從而構(gòu)建出靶蛋白蛋白相互作用（PPI）、單一成分-靶點-生物學(xué)通路網(wǎng)絡(luò)。分子對接及分子動力學(xué)模擬結(jié)果顯示，甘草查爾酮A與PPI網(wǎng)絡(luò)圖中度值最高的20個靶蛋白均能很好地結(jié)合，其中結(jié)合性最好的3個靶蛋白分別為視網(wǎng)膜母細胞瘤相關(guān)蛋白、環(huán)氧合酶2和丁酰膽堿酯酶。結(jié)論 從分子層面對甘草查爾酮A治療AD作用機制進行初步探討，揭示潛在的生物學(xué)機制，為其應(yīng)用提供理論依據(jù)。

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.

R926

科技部重大專項（2020071620211）