基于分子对接和网络药理学的大麻治疗帕金森病的作用机制研究

Mechanism of Cannabis Sativa in Treatment of Parkinson’s Disease based on Molecular Docking and Network Pharmacology

利用网络药理学和分子对接技术方法,探究大麻治疗帕金森病(Parkinson disease,PD)的主要活性成分、潜在靶点和作用机理。通过检索Pubmed、CNKI、TCMSP、Swiss ADME等数据库获取并筛选大麻活性成分,成分录入Swiss Target Prediction和Targetnet数据库预测相关作用靶点;采用Drug Bank、OMIM、Genecards和Dis Ge NET数据库收集PD相关靶点信息,与大麻活性成分靶点取交集,导入STRING数据库获得蛋白互作数据;Omicshare平台对有效作用靶点进行GO功能和KEGG通路富集分析;借助Cytoscpe 3.7.2软件构建大麻药物-成分-靶点网络,蛋白-蛋白互作(PPI)网络;最后,通过Auto Dock4.2和Py Mol软件对主要活性成分和关键靶点进行分子对接预测。最终,筛选获得大麻活性成分40个,其中核心成分15个;药物靶点210个,PD靶点1 254个,药物-疾病共同靶点51个,关键靶点5个,主要参与调解AGE-RAGE、HIF-1、TNF、VEGF等信号通路。分子对接结果提示,主要成分与核心靶点结合能在-4.47~-6.38,结合能力良好。该研究通过网络药理学和分子对接分析,探析了大麻治疗PD的潜在靶点和机制,为大麻治疗PD提供参考与借鉴。

In this paper,the bioactive components,potential targets and mechanisms of Cannabis sativa in the treatment of Parkinson’s disease( PD) were studied via network pharmacology and molecular docking analysis. Public databases including Pubmed、CNKI、TCMSP and Swiss ADME were used to obtain and screen the active components of hemp,and their bioactive ingredients and putative targets were then predicted through a search of the Swiss target prediction and target net databases. In addition,the targets of PD were obtained from Drug Bank、OMIM、Genecards and Dis Ge NET database. Meanwhile,the protein-protein interaction( PPI) data of hemp active components and PD common targets were obtained by STRING database. GO function and KEGG pathway enrichment were analysed by Omicshare plat form. Cytoscape3. 7. 2 software was used to construct the "cannabis-compounds-targets"network and PPI network for elucidating the comprehensive molecular mechanism of hemp against PD. Finally,molecular docking was carried out between the main active components of hemp and hub targets with Autodock 4. 2 and Py MOL software. Through literature review and screening,40 active components of hemp were obtained,and network pharmacological analysis of hemp in the treatment of PD,identified 15 active components with important biological effect. A total of 210 drug targets,1 254 PD targets,51 drug disease common targets,15 core components and 5 key targets were screened,and they were found to be enriched in a series of signaling pathways,such as AGE-RAGE、HIF-1、TNF and VEGF signaling pathways. Moreover,molecular docking analysis showed that the main ingredients were tightly bound to the core targets,and the binding energy was-4. 47 ~-6. 38. Based on network pharmacology and molecular docking analysis,the present study provides insights into the potential mechanism of hemp in PD after successfully screening for associated key target genes and signaling pathways. These findings provided a theoretical basis for further pharmacological research into the potential mechanism of hemp in PD.