药学学报, 2016, 51(5): 725-731
引用本文:
庞晓丛, 王喆, 方坚松, 连雯雯, 赵嬴, 康德, 刘艾林, 杜冠华. 治疗阿尔茨海默病的中药有效成分的网络药理学研究[J]. 药学学报, 2016, 51(5): 725-731.
PANG Xiao-cong, WANG Zhe, FANG Jian-song, LIAN Wen-wen, ZHAO Ying, KANG De, LIU Ai-lin, DU Guan-hua. Network pharmacology study of effective constituents of traditional Chinese medicine for Alzheimer's disease treatment[J]. Acta Pharmaceutica Sinica, 2016, 51(5): 725-731.

治疗阿尔茨海默病的中药有效成分的网络药理学研究
庞晓丛, 王喆, 方坚松, 连雯雯, 赵嬴, 康德, 刘艾林, 杜冠华
中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
为了探索用于治疗阿尔茨海默病的中药方剂的网络药理学, 本文收集了阿尔茨海默病相关的25 个作用靶点以及13 种治疗阿尔茨海默病中药方剂, 根据单味药出现的频率, 从中选取了7 种代表性的中草药进行后续研究。利用已建立的机器学习分类模型对中草药的化学成分进行作用靶点预测, 并构建了化合物-靶点网络、靶点-靶点网络及靶点-疾病网络来解释中药方剂的多种有效成分的协同作用机制。此外, 经过血脑屏障透过性分析及对预测靶点的验证, 得到了7 个具有代表性结构的多靶点的先导化合物。本文应用网络药理学研究了抗阿尔茨海默病的传统中草药有效成分的网络作用机制, 为抗阿尔茨海默病的中药临床应用及多靶点药物设计提供了重要信息。
关键词:    阿尔茨海默病      中药方剂      网络药理学      虚拟筛选      类药性     
Network pharmacology study of effective constituents of traditional Chinese medicine for Alzheimer's disease treatment
PANG Xiao-cong, WANG Zhe, FANG Jian-song, LIAN Wen-wen, ZHAO Ying, KANG De, LIU Ai-lin, DU Guan-hua
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
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.
Key words:    Alzheimer disease    Chinese medicinal formulae    network pharmacology    virtual screening    drug-likeness   
收稿日期: 2015-10-09
DOI: 10.16438/j.0513-4870.2015-0950
基金项目: 国家重大新药创制科技重大专项(2014ZX09507003-002, 2013ZX09508104001002);国际合作项目(2011DFR31240);国家863计划(2014AA021101).
通讯作者: 刘艾林, Tel/Fax: 86-10-83150885, E-mail: liuailin@imm.ac.cn;杜冠华, Tel/Fax: 86-10-63165184, E-mail: dugh@imm.ac.cn
Email: liuailin@imm.ac.cn;dugh@imm.ac.cn
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