基于网络药理学石菖蒲挥发油干预中枢神经系统疾病共性物质基础和作用机制探讨

Exploring common material basis and mechanism of volatile oil from Acori Tatarinowii Rhizoma in intervening central nervous system diseases based on network pharmacology

目的:探究石菖蒲挥发油成分干预阿尔茨海默病、帕金森病、癫痫和抑郁症4种中枢神经系统疾病的共性物质基础及其作用机制。方法:通过检索TCMSP、PubChem和CNKI数据库收集石菖蒲的挥发油成分,通过SwissADME平台筛选高吸收、可透过血脑屏障且具有类药性的成分;利用SwissTargetPrediction、BATMAN-TCM、GeneCards和OMIM数据库分别预测活性成分和治疗4种疾病的潜在靶点;通过Cytoscape 3.6.0构建“挥发油成分-靶点-疾病”网络;基于STRING数据库和BioGRID数据库构建潜在靶点的蛋白质-蛋白质相互作用(PPI)网络;利用Bioconductor数据库和R 4.1.2软件进行潜在靶点的GO功能注释和KEGG富集分析;最后运用AutoDock Vina软件对关键靶点和关键成分进行分子对接验证。结果:从石菖蒲中共筛选得到33个挥发油活性成分及61个靶点。“成分-靶点-疾病”网络显示α-香附酮、菖蒲螺烯酮、马兜铃酮、异水菖酮、菖蒲螺酮烯、水菖蒲酮、桔利酮和异丁香酚甲醚为干预疾病的关键成分。PPI网络显示AKT1、TP53和mTOR为关键靶点,分子对接结果显示各关键靶点与关键成分的结合能均<-4.7 kcal/mol。KEGG富集结果显示多巴胺能突触通路、帕金森病通路、羟色胺能突触通路、阿尔茨海默病通路为关键通路。结论:从石菖蒲中筛选出8种挥发油有效成分,其可能通过调控靶点AKT1、TP53和mTOR参与多个通路对中枢神经系统疾病发挥治疗作用。

Objective:To explore the common material basis of volatile oil from Acori Tatarinowii Rhizoma and mechanism in intervening Alzheimer’s disease,Parkinson’s disease,epilepsy and depression based on network pharmacology.Methods:The volatile oil components of Acori Tatarinowii Rhizoma were obtained from TCMSP,PubChem and CNKI databases. And the components with high absorption,blood-brain barrier and drug-like properties were screened by SwissADME platform. The active components and potential targets in the treatment of 4 diseases were predicted through SwissTargetPrediction,BATMAN-TCM,GeneCards and OMIM databases.Thus,the“components-targets-diseases”network was constructed by Cytoscape 3.6.0. The protein-protein interaction(PPI)network of potential targets was constructed based on the STRING and BioGRID databases. The GO function annotation and KEGG enrichment analysis of potential targets were performed by Bioconductor database and R 4.1.2 software. Finally,AutoDock Vina was used to validate the molecular docking of key targets and key components.Results:Totally 33 volatile oil active components from Acori Tatarinowii Rhizoma and 61 corresponding targets were obtained. The“components-targets-diseases”network showed that α-cyperone,acorenone,aristolone,isoshyobunone,acoronene,shyobunone,zierone and methyl isoeugenol were the key components in disease intervention. PPI network showed that AKT1,TP53 and mTOR were the key targets. The molecular docking results showed that the binding energies of key targets and key compounds were less than-4.7 kcal/mol. KEGG enrichment results showed that dopaminergic synapse pathway,Parkinson’s disease pathway,serotonergic synapse pathway,Alzheimer’s disease pathway were the key pathways.Conclusion:Eight volatile oil active components were screened from Acori Tatarinowii Rhizoma,which may exert the therapeutic effects on central nervous system diseases by participating in multiple pathways through regulatory targets AKT1,TP53 and mTOR.