Network pharmacology is a powerful tool to reflect the pharmacologically active effects,mechanism of action and toxic activity of traditional Chinese medicines(TCMs).The ingredients of TCMs,associated with quality con...Network pharmacology is a powerful tool to reflect the pharmacologically active effects,mechanism of action and toxic activity of traditional Chinese medicines(TCMs).The ingredients of TCMs,associated with quality control of TCM products,are those fundamental chemicals that exhibit biological activities.A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs,though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous.Now some methods and technologies must be applied to predict and explore the quality marker(Q-marker)for quality control,as well as to clarify the factors affecting the quality of TCM,which may give new insight into rational ground of establishment of appropriate quality control and assessment system.In this review paper,authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects:(1)from network medicine to network pharmacology,(2)complex network system of traditional Chinese medicine,and(3)predicting TCM quality markers based on network pharmacology.Authors proposed the research pattern on network pharmacology based on biological and medical networks,and further TCM network pharmacology based on substantial basis of TCM formulae,and the idea of"effect-ingredient-target-fingerprint"to predict and recognize the TCM Qmarker was the ultimate goal.In addition,authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.展开更多
The inception of network pharmacology comes from the advance in ＂multi-target, multi-drug＂ paradigm and opens up a new field for pharmaceutical science. Traditional Chinese medicine （TCM） is well-known for its use...The inception of network pharmacology comes from the advance in ＂multi-target, multi-drug＂ paradigm and opens up a new field for pharmaceutical science. Traditional Chinese medicine （TCM） is well-known for its use of medicinal herb combinations to treat the functional disorders induced by diseases through a holistic view, which naturally followed the principal of network pharmacology. In this review, the methodologies of network pharmacology in TCM studies were summarized. Specifically, the methodologies for network construction and network analysis were discussed in detail by following several TCM study cases. The perspectives for TCM network pharmacology were also provided.展开更多
目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中...目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中插件分析获得关键靶点,构建生物学总调控网络,并对其进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;分子对接评价补骨脂酚与潜在关键靶点结合的亲和力。结果共获得补骨脂酚靶点3952个,肝毒性基因6025个和交集基因2221个。经分析,补骨脂酚主要作用于TP53、HSP90AA1、EP300等关键靶点,参与氧化应激反应与细胞增殖、分化、凋亡过程的调控,涉及多种酶调控等生物过程,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。补骨脂酚与EP300、HSP90AA1靶点的亲和力最强,能够与二者的结合口袋形成较强的疏水作用,total score值为8.8582、7.2178。结论补骨脂酚致肝毒性具有多靶点、多途径的作用规律,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。展开更多
Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines(TCMs).In this study,we reviewed the application o...Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines(TCMs).In this study,we reviewed the application of network toxicology based on LC-MS metabolomics,mainly in the study of toxic components and the toxicity mechanism of TCMs,which provides new ideas and methods for the further study of the toxicity mechanism of TCMs.展开更多
目的:通过建立草乌活性成分-作用靶点、蛋白相互作用、靶点相应的生物功能和通路网络,以及利用分子对接技术探讨草乌心脏毒性的作用机制。方法:通过中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology,...目的:通过建立草乌活性成分-作用靶点、蛋白相互作用、靶点相应的生物功能和通路网络,以及利用分子对接技术探讨草乌心脏毒性的作用机制。方法:通过中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)和毒性与基因比较数据库(Comparative Toxicogenomics Database,CTD)筛选出草乌有毒候选成分。依据反向药效团匹配(Pharm Mapper)方法预测草乌毒性候选成分的作用靶点,与从人类基因数据库(Gene Cards)中寻找到的心脏相关基因蛋白进行比对,筛选出重合的蛋白作为草乌的潜在的心脏毒性靶点。采用Cytoscape软件构建草乌毒性候选成分-作用靶点网络。通过String数据库结合Cytoscape软件绘制蛋白相互作用网络,用DAVID平台对靶点生物功能及涉及的通路进行分析,最后用Discover Studio软件对关键蛋白与草乌毒性候选成分的结合进行验证。结果:草乌中筛选得到6种有毒候选成分,涉及27个心脏毒性作用靶点,网络分析结果表明靶点主要是通过参与心脏磷代谢,磷酸化的监管等磷相关的代谢和调节,以及通过FKBP1A,TGFB2,INSR等靶点对心脏的代谢,发育及形态产生重要的影响,进而产生心脏毒性。结论:利用中药多成分-多靶点-多通路的特点,探究了草乌心脏毒性作用机制,并预测了其可能存在的毒性,为进一步开展草乌心脏毒性作用机制研究提供了新思路和新方法。展开更多
基金supported by National Nature Science Foundation for Key Projects(No.81430096)National New Drug Innovation(No.2017ZX09301062.)Tianjin Science and Technology Plan Project(No.19YFSLQY00110).
文摘Network pharmacology is a powerful tool to reflect the pharmacologically active effects,mechanism of action and toxic activity of traditional Chinese medicines(TCMs).The ingredients of TCMs,associated with quality control of TCM products,are those fundamental chemicals that exhibit biological activities.A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs,though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous.Now some methods and technologies must be applied to predict and explore the quality marker(Q-marker)for quality control,as well as to clarify the factors affecting the quality of TCM,which may give new insight into rational ground of establishment of appropriate quality control and assessment system.In this review paper,authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects:(1)from network medicine to network pharmacology,(2)complex network system of traditional Chinese medicine,and(3)predicting TCM quality markers based on network pharmacology.Authors proposed the research pattern on network pharmacology based on biological and medical networks,and further TCM network pharmacology based on substantial basis of TCM formulae,and the idea of"effect-ingredient-target-fingerprint"to predict and recognize the TCM Qmarker was the ultimate goal.In addition,authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.
基金National Basic Research Program of China(2012CB518405)National Natural Science Foundation of China(81373893)
文摘The inception of network pharmacology comes from the advance in ＂multi-target, multi-drug＂ paradigm and opens up a new field for pharmaceutical science. Traditional Chinese medicine （TCM） is well-known for its use of medicinal herb combinations to treat the functional disorders induced by diseases through a holistic view, which naturally followed the principal of network pharmacology. In this review, the methodologies of network pharmacology in TCM studies were summarized. Specifically, the methodologies for network construction and network analysis were discussed in detail by following several TCM study cases. The perspectives for TCM network pharmacology were also provided.
文摘目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中插件分析获得关键靶点,构建生物学总调控网络,并对其进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;分子对接评价补骨脂酚与潜在关键靶点结合的亲和力。结果共获得补骨脂酚靶点3952个,肝毒性基因6025个和交集基因2221个。经分析,补骨脂酚主要作用于TP53、HSP90AA1、EP300等关键靶点,参与氧化应激反应与细胞增殖、分化、凋亡过程的调控,涉及多种酶调控等生物过程,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。补骨脂酚与EP300、HSP90AA1靶点的亲和力最强,能够与二者的结合口袋形成较强的疏水作用,total score值为8.8582、7.2178。结论补骨脂酚致肝毒性具有多靶点、多途径的作用规律,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。
基金supported by National Science Foundation for Post-doctoral(2015M570231)Science and Technology Program of Tianjin(15PTCYSY00030)National Key research and development program(2016YFE0121400).
文摘Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines(TCMs).In this study,we reviewed the application of network toxicology based on LC-MS metabolomics,mainly in the study of toxic components and the toxicity mechanism of TCMs,which provides new ideas and methods for the further study of the toxicity mechanism of TCMs.
文摘目的:通过建立草乌活性成分-作用靶点、蛋白相互作用、靶点相应的生物功能和通路网络,以及利用分子对接技术探讨草乌心脏毒性的作用机制。方法:通过中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)和毒性与基因比较数据库(Comparative Toxicogenomics Database,CTD)筛选出草乌有毒候选成分。依据反向药效团匹配(Pharm Mapper)方法预测草乌毒性候选成分的作用靶点,与从人类基因数据库(Gene Cards)中寻找到的心脏相关基因蛋白进行比对,筛选出重合的蛋白作为草乌的潜在的心脏毒性靶点。采用Cytoscape软件构建草乌毒性候选成分-作用靶点网络。通过String数据库结合Cytoscape软件绘制蛋白相互作用网络,用DAVID平台对靶点生物功能及涉及的通路进行分析,最后用Discover Studio软件对关键蛋白与草乌毒性候选成分的结合进行验证。结果:草乌中筛选得到6种有毒候选成分,涉及27个心脏毒性作用靶点,网络分析结果表明靶点主要是通过参与心脏磷代谢,磷酸化的监管等磷相关的代谢和调节,以及通过FKBP1A,TGFB2,INSR等靶点对心脏的代谢,发育及形态产生重要的影响,进而产生心脏毒性。结论:利用中药多成分-多靶点-多通路的特点,探究了草乌心脏毒性作用机制,并预测了其可能存在的毒性,为进一步开展草乌心脏毒性作用机制研究提供了新思路和新方法。
