基于网络药理学对白术治疗阿尔茨海默症的机制探讨  

Mechanism of atractylodes for Alzheimer’s disease based on network pharmacology

作　　者：胡倩 刘育铖[1,2] 毛思宇 冯星 HU Qian;LIU Yu-cheng;MAO Si-yu;FENG Xing(School of Medicine,Hunan Normal University,Changsha 410013;Key Laboratory of Small Targeted Molecules of Hunan,Department of Pharmacy,School of Medicine,Hunan Normal University,Changsha 410013)

机构地区：[1]湖南师范大学医学院,长沙410013 [2]湖南师范大学小分子靶向药物研究与创制湖南省重点实验室,长沙410013

出　　处：《中南药学》2020年第3期427-434,共8页Central South Pharmacy

基　　金：湖南省自然科学基金面上项目(No.2017JJ2188);湖南省教育厅重点项目(No.16A128);长沙市科技局一般项目(No.Kq1907126,Kq1701052);化学生物学及中药分析教育部重点实验室开放基金课题(No.KLCBTCMR18-04)。

摘　　要：目的利用网络药理学探讨中药白术"成分-靶标-疾病"的相互关系及其有效成分治疗阿尔茨海默症的作用机制。方法从中药系统药理学数据库(TCMSP)中筛选白术活性成分,利用Cytoscape 3.2.1软件将活性成分、成分靶标及相关疾病构建可视化网络图,通过生物信息学方法进行关键靶标的GO功能分析和KEGG信号通路富集分析;并通过MTT细胞增殖实验与活性氧(ROS)荧光探针实验验证白术有效成分对损伤神经细胞的保护作用。结果通过网络药理学方法收集到白术共55个化学成分,进一步筛选出18个活性成分,其中包括主要有效成分双白术内酯。网络富集得到17个关键靶标,72种相关疾病及5条通路。这些成分靶标,疾病靶标和信号通路均表明白术可以有效作用于阿尔茨海默症。细胞实验表明白术的有效成分双白术内酯能显著提高损伤神经细胞的细胞活力,并减少活性氧的生成。结论本研究筛选了白术的有效成分、关键靶标及相关通路,为其治疗阿尔茨海默症的作用机制研究提供了科学依据。Objective To explore the relationship between component target-disease in atractylodes and treatment mechanism of its active compounds for Alzheimer’s disease based on network pharmacology. Methods Traditional Chinese medicine system pharmacology(TCMSP) database was applied to screen out the active compounds of atractylodes. Cytoscape 3.2.1 software was used to construct the visual network diagrams of active compounds and related diseases. The KEGG signal pathway enrichment analysis of key targets was performed by bioinformatics methods. In order to verify the protective effects of the active compounds of atractylodes on injured nerve cells, MTT cell experiments and reactive oxygen species fluorescent experiments were used. Results Totally 55 compounds of atractylodes were collected by network pharmacology, and 18 active compounds were screened out, including biatractylolide. The network enriched 17 targets as key targets 72 related diseases and 5 pathways. These compounds targets, disease targets and signaling pathways indicated that atractylodes effectively acted on Alzheimer’s disease. Cell experiments showed that biatractylolide significantly increased the cell viability of the injured nerve cells and reduced the production of reactive oxygen species. Conclusion This study screens out the key targets and related pathways of atractylodes, providing a theoretical basis for the treatment mechanism in Alzheimer’s disease.

关 键 词：网络药理学 白术 阿尔茨海默症 关键靶标 双白术内酯 

分 类 号：R286[医药卫生—中药学]