基于网络药理学和分子对接探讨甘草防治阿尔茨海默病的分子机制

Molecular mechanism of Glycyrrhiza in prevention and treatment of Alzheimer’s disease based on network pharmacology and molecular docking

目的运用网络药理学和分子对接技术探究甘草防治阿尔茨海默病(AD)的分子机制。方法通过中药系统药理学数据库与分析平台(TCMSP)筛选甘草活性成分,并利用有关数据库筛选AD相关靶点。以Cytoscape软件构建"药物-化合物-靶点"网络,并用分子对接验证有效成分与靶点亲和力。结果筛选出甘草64个活性成分和692个靶点,这些靶点与82个AD相关潜在靶点有较强相互作用,主要富集于神经活性配体受体相互作用、AD通路、钙信号通路、5-羟色胺能突触、cAMP信号通路等12条通路。分子对接结果显示甘草素、光甘草素和甘草宁O等化合物与关键靶点淀粉样前体蛋白(APP)、单胺氧化酶B(MAOB)、半胱天冬蛋白酶3(CASP3)、5-羟色胺转运体(SLC6A4)、乙酰胆碱酯酶(AchE)具有良好亲和力。结论甘草中异甘草素、甘草素等化合物可能通过作用于APP、CASP3、MAOB、SLC6A4、ACHE等靶点,介导5-羟色胺能突触通路,进而发挥防治AD作用。

Objective To explore the molecular mechanism of Glycyrrhiza in prevention and treatment of Alzheimer’s disease(AD)using network pharmacology and molecular docking.Methods The active components of Glycyrrhiza were screened by the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).AD-associated targets were screened using related databases.The drug-compound-target network was constructed by Cytoscape software,and the affinity between effective components and targets was verified by molecular docking.Results Sixty-four active components and 692 targets of Glycyrrhiza were screened.These targets had strong interaction with 82 potential ADassociated targets,mainly enriched in 12 pathways,such as neuroactive ligand-receptor interaction,AD pathway,calcium signaling,serotonergic synapse,cAMP signaling and so on.The molecular docking revealed that glycyrrhizin,glabrene and gancaonin O had good affinity with key targets amyloid precursor protein(APP),monoamine oxidase B(MAOB),caspase-3,SLC6 A4 and AchE.Conclusion Glycyrrhiza compounds such as isoliquiritigenin and glycyrrhizin may prevent and treat AD by acting on APP,caspase-3,MAOB,SLC6 A4 and AchE and mediating serotonergic synaptic pathway.