| Biological sciences & biotechnology |
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| Application of connectivity map technology in traditional Chinese medicines |
| ZHANG Xiaofang, KANG Yongbo, SU Junhong, KONG Xiangyang* |
| Genetics and Pharmacogenomics Laboratory, Medical School, Kunming University of Science and Technology, Kunming 650500, China |
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Abstract Connectivity map (CMap) technology was initially developed in Broad Institute of Massachusetts Institute of Technology and Harvard. It has been widely used to investigate mechanism of action of drug by academic research institutes and pharmaceutical companies globally. CMap technology, as one of the most important techniques in genomic era, provides a large public database of gene expression profiles and reveals how drugs affect gene expression under disease conditions. CMap database contained 1 309 FDA-approved small molecules and these small molecules were tested in five human cell lines to generate over 7 000 gene expression profiles. It also provided an interactive website and an online tool to conduct CMap queries against the chemical reference catalogues (http://www.broadinstitute.org/cmap). Application of CMap technology in research on traditional Chinese medicines (TCMs) offers new avenues for understanding TCMs in terms of efficacy, dosage and safety. Since a prescribed TCM have complicated composition, it may exert therapeutic effects by a collective and interactive manner of the contained variety of compounds. Additionally, TCM often clashes with the knowledge of contemporary medicine, because its principles and concepts are difficult to be understood by scientists with background in contemporary medicine. For these reasons, using the usual “drug-target” measurement technology is difficult for comprehensive analysis of the mechanism of action of TCMs, resulting in less competitive of TCMs in international market. CMap technology is a gene expression signature-based approach and of a unique power for studying drugs with complex ingredients such as TCMs. By querying CMap database with a gene expression profile of TCM and comparing its similarity with CMap compounds, a list of ranked drugs can be obtained, which may provide clues for connections between the CMap drugs and TCM for sharing mechanism of action, chemical and physiological processes, and therapeutic potentials for particular diseases. In this article, we reviewed the advances in our understanding of application of the CMap technology for research on TCM, in respect to the mechanism of action, the drug repositioning and identification of active ingredients of TCM. In terms of the mechanism of TCMs, CMap technology is of potentials for predicting the efficacy and side effects of known TCMs and provides new ideas for further understanding of the biological pathways influenced under the treatment of TCMs. For application in drug repositioning, as CMap database achieves numerous existing drugs and their associated gene expression spectrums, it is possible to find new indications for TCMs by matching its gene expression profile to those in CMap database. Meanwhile, by comparing with the traditional thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC), CMap technology can be very useful for identifying active ingredients of TCMs. Up to date, CMap technology has been successfully used in several studies on TCMs. However, in respect to TCM research, there are limitations of the current CMap technology, in particular the limited number of CMap compounds available in the database. Thus, this genomic approach can be integrated with traditional chromatography-based fingerprinting method for better understanding of TCMs. Furthermore, it is important to establish CMap technology as the core platform for TCM research, including discovery of new TCMs and exploration of the new application of TCMs.
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Published: 20 September 2016
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Connectivity map技术在中药研究中的应用
Connectivity map (CMap)是基于RNA芯片研究药物作用机制和药物重定位的技术与数据资源,主要的优势在于能够高效地对全基因组上的基因表达做整体分析。相对于低通量的药理学、毒理学方法以及色谱技术,该技术能以全面、高通量、准确等优点广泛应用于药物研究。尤其对由多种化合物共同作用发挥疗效的中药,CMap 技术可以突破“药物—靶标”测定技术的单一性困难,对中药的作用机制做综合性分析,从分子水平上阐明中药的药物作用机制,有利于开发自主知识产权的中药,也为中药获取国际认可奠定理论基础。本文系统介绍CMap技术在中药研究方面的应用潜力,同时对该技术研究中药的作用机制、药物重定位及鉴别有效成分进行评价,还对推动中药走向国际市场做了具体分析与展望。
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