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

Xijun Wang*, Aihua Zhang, Ping Wang, Hui Sun, Gelin Wu, Wenjun Sun, Haitao Lv, Guozheng Jiao, Hongying Xu, Ye Yuan, Lian Liu, Dixin Zou, Zeming Wu, Ying Han, Guangli Yan, Wei Dong, Fangfang Wu, Tianwei Dong, Yang Yu, Shuxiang ZhangXiuhong Wu, Xin Tong, Xiangcai Meng

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

142 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1226-1238
Number of pages13
JournalMolecular and Cellular Proteomics
Volume12
Issue number5
Early online date29 Jan 2013
DOIs
Publication statusPublished - May 2013

Scopus Subject Areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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