Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry

Abstract

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 timecourse 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.

Ephedrae Herba and Cinnamomi Cortex interactions with G glycoprotein inhibit respiratory syncytial virus infectivity

“…Maoto is a multicomponent formulation extracted from four plants: Ephedrae Herba (EH), Cinnamomi Cortex (CC), Armeniacae Semen (AS), and Glycyrrhize Radix (GR) (Supplementary Table 1 ). The formulation contains over 350 compounds; the major active compounds are ephedrine, methylephedrine, hippuric acid, and glycyrrhetinic acid 25 , 26 . We previously reported the results of two clinical trials showing that maoto was tolerable and effective in treating seasonal influenza by comparison with neuraminidase inhibitors 27 , 28 .…”

Inhibition of respiratory syncytial virus infectivity by Ephedrae Herba and Cinnamomi Cortex through interaction with G glycoprotein

“…The formulation contains over 350 compounds; the major active compounds are ephedrine, methylephedrine, hippuric acid, and glycyrrhetinic acid 25,26 . We previously reported the results of two clinical trials showing that maoto was tolerable and effective in treating seasonal in uenza by comparison with neuraminidase inhibitors 27,28 .…”