Functional metabolomics innovates therapeutic discovery of traditional Chinese medicine derived functional compounds

Traditional Chinese medicines (TCMs) produce chemically diverse functional compounds that are importantly chemical resource for facilitating new drug discovery and development against a diversity of diseases. However, modern exploration of TCM derived functional compounds is significantly hindered by the inefficient elucidation of pharmacological functions over past decades, because conventional research methods are incapable of efficiently elucidating therapeutic potential of TCM conferred by multiple functional compounds. Functional metabolomics has the priority-capacity to characterize systems therapeutic actions of TCM by precisely capturing molecular interactions between disease response metabolite biomarkers (DRMB) and functional compounds (secondary metabolites), which underline pharmacological efficiency and associated therapeutic mechanisms. In this critical review, we innovatively summarize systems therapeutic feature of TCM derived functional compounds from a functional-metabolism perspective, then systems metabolic targets (SMT) identified by functional metabolomics method are strategically proposed to better understanding of therapeutic discovery of TCM derived functional compounds. In addition, we propose the perspective strategy as Spatial Temporal Operative Real Metabolomics (STORM) to considerably improve analytical capacity of functional metabolomics method by selectively incorporating the cutting edge technologies of mass spectrometry imaging, isotope-metabolic fluxomics, synthetic and biosynthetic chemistry, which could considerably enhance the precision and resolution of elucidating pharmacological efficiency and associated therapeutic mechanisms of TCM derived functional compounds. Collectively, such critical review is expected to provide novel perspective-strategy that could significantly improve modern exploration and exploitation of TCM derived functional compounds that further promote new drug discovery and development against the complex diseases. [Display omitted] •Therapeutic potential of TCM derived functional compounds is still overlooked due to the methodological limitation.•Functional metabolomics can identify and validate systems metabolic targets (SMT) of the diseases.•Functional metabolomics can decipher pharmacological efficiency of TCM derived functional compounds based on SMT.•A new spatial temporal operative real metabolomics (STORM) is proposed to innovate innova TCM derived functional compounds.