中药抗肿瘤作用的物质基础与网络机制研究(1)
摘要目的：為了探讨抗肿瘤中药复方的物质基础和网络药理机制，并且阐明中药方剂中各种有效成分的协同作用机理。方法：本文通过收集肿瘤防治相关的中药复方，并从中选取出现频次较高的单味药，使用CNPC和TCMSP数据库进行化学成分的收集，对有效化学成分进行了抗肿瘤作用的物质基础研究；利用TCMID及CTD数据库寻找化学成分的作用基因，在此基础上利用Cytoscape构建网络，进行网络机制研究。结果：收集了65个抗肿瘤中药复方，其中出现频次大于10的单味药有4个，分别为甘草、黄芪、人参和黄芩，其已知化学成分分别为172，70，293和92个，抗肿瘤有效成分主要包括三萜类、黄酮类、多糖类、皂苷类化合物。在化学成分相关基因分析的基础上，构建了化学成分—基因调控网络，蛋白质相互作用网络，基因通路富集网络以及基因疾病网络，以揭示中药复方的多种有效成分的协同作用机制。此外，应用分子对接方法，对化学成分影响较大的基因相关蛋白进行了相互作用分析，包括PTG2、EGFR、PPARG、ESR1、MTOR、AKT1、MAPK1、PPARA和MAPK8。大部分化合物都能作用于多个靶点，主要涉及生物碱、黄酮及其苷、有机酸及二蒽酮等结构类型，代表性的化学成分有水仙苷、芦丁、北豆根碱、黄岑素、汉黄芩甙、异夏佛塔苷、亚叶酸、伪金丝桃素等。结论：本文应用统计学方法、网络药理学方法及分子对接方法，初步揭示了抗肿瘤传统中草药有效成分及其网络作用机制，为中药抗肿瘤多靶点药物设计提供重要信息。
关键词肿瘤；中药；网络药理学；数据挖掘；分子对接
Network Pharmacologybased Study of the Active Constituents of Chinese Medicinal Formulae for Antitumor Mechanism
Zhang Baoyue1，Zheng Yifu2，Pang Xiaocong1，Zheng Xiangjin1，Wang Zhe1，Ding Hong2，Liu Ailin1，Du Guanhua1
(1 Institute of Materia Medica，Chinese Academy of Medical Sciences and Peking Union Medical College，Beijing 100050，China； 2 School of Pharmaceutical Sciences，Wuhan University，Wuhan 430072，China)
AbstractObjective：To investigate the network pharmacology of antitumor Chinese medicinal formulae and explain the synergistic mechanism of various active ingredients of Chinese medicinal formulae.Methods：We collected the antitumor Chinese medicinal formulae and chose several single herbs with the top frequency for further study.The chemical constituents of these herbs were downloaded from databases CNPC and Traditional Chinese Medicine Systems Pharmacology and were analyzed to set up the antitumor material basis.The genes regulated by these constituents were retrieved in Traditional Chinese Medicine integrated database and Comparative Toxicogenomics database.Results：We collected 65 antitumor Chinese medicinal formulae，and 4 single herbs were selected，including Radix Glycyrrhizae，Radix Astragali seu Hedysari，Radix Ginseng and Radix Scutel ariae，which consist of 172，70，293，and 92 known constituents，respectively.Antitumor active ingredients mainly included triterpenoids，flavonoids，polysaccharides，and saponin compounds.The constituentgene network，proteinprotein interaction network，genepathway enrichment network，and genedisease network were constructed based on chemical compositionrelated genetic analysis.Moreover，molecular docking was employed to clarify the interactions between active constituents and key drug targets (PTG2，epidermal growth factor receptor，peroxisome proliferatoractivated receptor gamma，estrogen receptor 1，mammalian target of rapamycin，AKT1，mitogenactivated protein kinase 1 (MAPK1)，peroxisome proliferatoractivated receptor alpha，and MAPK8).Most of the constituents could act on multiple targets，whose structures mainly belonged to alkaloids，flavonoids，and their glycosides，organic acids，or dianthrone，and their representative chemical constituents included narcissus glycosides，rutin，dauricine，scutellarin，baicalin，isoschaftoside，and leucovorin.Conclusion：The network mechanism of the effective constituents from traditional Chinese medicines (TCMs) for antitumor therapy was partially uncovered by using statistical methods，network pharmacology methods，and molecular docking methods.This study will provide important information for new drug design with multiple targets for antitumor therapy., http://www.100md.com(张宝月 郑一夫 庞晓丛)
关键词肿瘤；中药；网络药理学；数据挖掘；分子对接
Network Pharmacologybased Study of the Active Constituents of Chinese Medicinal Formulae for Antitumor Mechanism
Zhang Baoyue1，Zheng Yifu2，Pang Xiaocong1，Zheng Xiangjin1，Wang Zhe1，Ding Hong2，Liu Ailin1，Du Guanhua1
(1 Institute of Materia Medica，Chinese Academy of Medical Sciences and Peking Union Medical College，Beijing 100050，China； 2 School of Pharmaceutical Sciences，Wuhan University，Wuhan 430072，China)
AbstractObjective：To investigate the network pharmacology of antitumor Chinese medicinal formulae and explain the synergistic mechanism of various active ingredients of Chinese medicinal formulae.Methods：We collected the antitumor Chinese medicinal formulae and chose several single herbs with the top frequency for further study.The chemical constituents of these herbs were downloaded from databases CNPC and Traditional Chinese Medicine Systems Pharmacology and were analyzed to set up the antitumor material basis.The genes regulated by these constituents were retrieved in Traditional Chinese Medicine integrated database and Comparative Toxicogenomics database.Results：We collected 65 antitumor Chinese medicinal formulae，and 4 single herbs were selected，including Radix Glycyrrhizae，Radix Astragali seu Hedysari，Radix Ginseng and Radix Scutel ariae，which consist of 172，70，293，and 92 known constituents，respectively.Antitumor active ingredients mainly included triterpenoids，flavonoids，polysaccharides，and saponin compounds.The constituentgene network，proteinprotein interaction network，genepathway enrichment network，and genedisease network were constructed based on chemical compositionrelated genetic analysis.Moreover，molecular docking was employed to clarify the interactions between active constituents and key drug targets (PTG2，epidermal growth factor receptor，peroxisome proliferatoractivated receptor gamma，estrogen receptor 1，mammalian target of rapamycin，AKT1，mitogenactivated protein kinase 1 (MAPK1)，peroxisome proliferatoractivated receptor alpha，and MAPK8).Most of the constituents could act on multiple targets，whose structures mainly belonged to alkaloids，flavonoids，and their glycosides，organic acids，or dianthrone，and their representative chemical constituents included narcissus glycosides，rutin，dauricine，scutellarin，baicalin，isoschaftoside，and leucovorin.Conclusion：The network mechanism of the effective constituents from traditional Chinese medicines (TCMs) for antitumor therapy was partially uncovered by using statistical methods，network pharmacology methods，and molecular docking methods.This study will provide important information for new drug design with multiple targets for antitumor therapy., http://www.100md.com(张宝月 郑一夫 庞晓丛)