Introduction: Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential.
Objective: The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans.
Methods: We performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis.
Results: About 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles.
Conclusion: The results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM.
Keywords: Kampo medicine; Metabolite annotation; Metabolomics; Natural products; Traditional herbal medicine.