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

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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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          Author and article information

          Journal
          Mol Cell Proteomics
          Molecular & cellular proteomics : MCP
          American Society for Biochemistry & Molecular Biology (ASBMB)
          1535-9484
          1535-9476
          May 2013
          : 12
          : 5
          Affiliations
          [1 ] National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, Heilongjiang University of Chinese Medicine and Key Pharmacometabolomic Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China. xijunwangls@126.com
          Article
          S1535-9476(20)31106-3
          10.1074/mcp.M112.021683
          3650334
          23362329
          121de312-84e9-4069-add5-0e7f7afe81e3
          History

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