Pang Xiao-cong, Wang Zhe, Fang Jian-song, Lian Wen-wen, Zhao Ying, Kang De, Liu Ai-lin, Du Guan-hua
Yao Xue Xue Bao. 2016 May;51(5):725-31.
This study aims to investigate the network pharmacology of Chinese medicinal formulae for treatment of Alzheimer’s disease.Machine learning algorithms were applied to construct classifiers in predicting the active molecules against 25 key targets toward Alzheimer’s disease(AD).By extensive data profiling, we compiled 13 classical traditional Chinese medicine(TCM) formulas with clinical efficacy for AD. There were 7 Chinese herbs with a frequency of 5 or higher in our study. Based on the predicted results, we built constituent-target, and further construct target-target interaction network by STRING(Search Tool for the Retrieval of Interacting Genes/Proteins) and target-disease network by DAVID(Database for Annotation,Visualization and Integrated Discovery) and gene disease database to study the synergistic mechanism of the herbal constituents in the Chinese traditional patent medicine. By prediction of blood-brain penetration and validation by TCMsp (traditional Chinese medicine systems pharmacology) and Drugbank, we found 7 typical multi-target constituents which have diverse structure. The mechanism uncovered by this study may offer a deep insight into the action mechanism of TCMs for AD. The predicted inhibitors for the AD-related targets may provide a good source of new lead constituents against AD.
本研究旨在探讨用于治疗阿尔茨海默病的中药方剂的网络药理学。应用机器学习算法构建分类器,以预测针对阿尔茨海默病(AD)25个关键靶点的活性分子。通过广泛的数据剖析,我们整理了13个对AD具有临床疗效的经典中药方剂。在我们的研究中,有7味中药出现频率为5次或更高。基于预测结果,我们构建了成分-靶点网络,并通过STRING(搜索相互作用基因/蛋白质的工具)进一步构建靶点-靶点相互作用网络,通过DAVID(注释、可视化和综合发现数据库)和基因疾病数据库构建靶点-疾病网络,以研究中药复方中草本成分的协同作用机制。通过血脑屏障通透性预测,并经中药系统药理学数据库(TCMsp)和药物银行(Drugbank)验证,我们发现了7种结构各异的典型多靶点成分。本研究揭示的机制可能为深入了解中药治疗AD的作用机制提供见解。预测得到的AD相关靶点抑制剂可能为抗AD新的先导成分提供良好来源。