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.

中文翻译：

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转换代谢物（DAC-Met）的差异注释：使用高分辨率质谱法在血浆中探索从毛托（Ma-huang-tang）衍生的代谢物。

简介传统草药（THM）包含大量具有不同程度药理活性的天然化合物。为了阐明作用方式，在给予THM之前和之后血浆中全面的代谢产物谱分析至关重要。目的本研究的目的是探索和鉴定/注释在人类中施用THM后转化的代谢产物。方法我们对日本传统的汉方药物毛oto（ma-huang-tang）给药前后收集的人血浆进行了非靶向代谢组分析。然后根据DAC-Met策略选择和注释从毛豆衍生的代谢物，这是一种注释方法，它使用检测到的峰之间主要代谢反应的质量差异和差异网络分析。结果发现约80％的毛源成分是转化形式。DAC-Met之后，确定了15种以前未鉴定的代谢物的结构，随后用真实的标准物确认了其中5种。使用已发表的文献，我们还重建了人体内毛托成分的代谢途径。动力学时程分析揭示了他们多样化的动力学概况。结论结果表明，使用DAC-Met策略在血浆中进行时间分辨的综合代谢产物分析对阐明THM的复杂性非常有用。我们还重建了人类毛细胞成分的代谢途径。动力学时程分析揭示了他们多样化的动力学概况。结论结果表明，使用DAC-Met策略在血浆中进行时间分辨的综合代谢产物分析对阐明THM的复杂性非常有用。我们还重建了人类毛细胞成分的代谢途径。动力学时程分析揭示了他们多样化的动力学概况。结论结果表明，使用DAC-Met策略在血浆中进行时间分辨的综合代谢产物分析对阐明THM的复杂性非常有用。