Metabolomics Coupled with Proteomics Advancing Drug Discovery Towards more Agile Development of Targeted Combination Therapies

Abstract
To enhance therapeutic efficacy and reduce adverse effects of traditional Chinese medicine (TCM), practitioners often prescribe a combination 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 (YCHT), a classical formula and has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The three principal components of YCHT 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 that underlie 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 HI. 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.

The article is published online in Molecular & Cellular Proteomics and is free to access.