Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

Wang, Xijun, Zhang, Aihua, Wang, Ping, Sun, Hui, Wu, Gelin, Sun, Wenjun, Lv, Haitao, Jiao, Guozheng, Xu, Hongying, Yuan, Ye, Liu, Lian, Zou, Dixin, Wu, Zeming, Han, Ying, Yan, Guangli, Dong, Wei, Wu, Fangfang, Dong, Tianwei, Yu, Yang, Zhang, Shuxiang, Wu, Xiuhong, Tong, Xin, & Meng, Xiangcai (2013) Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies. Molecular and Cellular Proteomics, 12(5), pp. 1226-1238.

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Abstract

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

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ID Code: 62102
Item Type: Journal Article
Refereed: Yes
DOI: 10.1074/mcp.M112.021683
ISSN: 1535-9484
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 02 Sep 2013 23:30
Last Modified: 11 Apr 2017 01:57

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