Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota
The importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion tr...
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MDPI AG
2020-01-01
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author | Ran Peng Shu-Rong Ma Jie Fu Pei Han Li-Bin Pan Zheng-Wei Zhang Hang Yu Yan Wang |
author_facet | Ran Peng Shu-Rong Ma Jie Fu Pei Han Li-Bin Pan Zheng-Wei Zhang Hang Yu Yan Wang |
author_sort | Ran Peng |
collection | DOAJ |
description | The importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion trap time-of-flight multistage mass spectrometry (LC-MS/MS and LC/MS<sup>n</sup>-IT-TOF), four metabolites of triptolide (M1, M2, M3, and M4) were found in the intestinal contents of rats. M1 and M2, were isomeric monocarbonyl-hydroxyl-substituted metabolites with molecular weights of 390. M3 and M4 were isomeric dehydrogenated metabolites with molecular weights of 356. Among the four metabolites, the dehydrogenated metabolites (M3 and M4) were reported in the gut microbiota for the first time. The metabolic behaviors of triptolide in the gut microbiota and liver microsomes of rats were further compared. The monocarbonyl-hydroxyl-substituted metabolites (M1 and M2) were generated in both systems, and another monohydroxylated metabolite (M5) was found only in the liver microsomes. The combined results suggested that the metabolism of triptolide in the gut microbiota was specific, with two characteristic, dehydrogenated metabolites. This investigation might provide a theoretical basis for the elucidation of the metabolism mechanism of triptolide and guide its proper application in clinical administration. |
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spelling | doaj.art-bf1fa50013944f179ec9b4d43ecbe6aa2022-12-21T23:53:43ZengMDPI AGMolecules1420-30492020-01-0125360610.3390/molecules25030606molecules25030606Transforming of Triptolide into Characteristic Metabolites by the Gut MicrobiotaRan Peng0Shu-Rong Ma1Jie Fu2Pei Han3Li-Bin Pan4Zheng-Wei Zhang5Hang Yu6Yan Wang7State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaThe importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion trap time-of-flight multistage mass spectrometry (LC-MS/MS and LC/MS<sup>n</sup>-IT-TOF), four metabolites of triptolide (M1, M2, M3, and M4) were found in the intestinal contents of rats. M1 and M2, were isomeric monocarbonyl-hydroxyl-substituted metabolites with molecular weights of 390. M3 and M4 were isomeric dehydrogenated metabolites with molecular weights of 356. Among the four metabolites, the dehydrogenated metabolites (M3 and M4) were reported in the gut microbiota for the first time. The metabolic behaviors of triptolide in the gut microbiota and liver microsomes of rats were further compared. The monocarbonyl-hydroxyl-substituted metabolites (M1 and M2) were generated in both systems, and another monohydroxylated metabolite (M5) was found only in the liver microsomes. The combined results suggested that the metabolism of triptolide in the gut microbiota was specific, with two characteristic, dehydrogenated metabolites. This investigation might provide a theoretical basis for the elucidation of the metabolism mechanism of triptolide and guide its proper application in clinical administration.https://www.mdpi.com/1420-3049/25/3/606triptolidegut microbiotaliver microsomemetaboliteslc-ms/mslc/ms<sup>n</sup>-it-tof |
spellingShingle | Ran Peng Shu-Rong Ma Jie Fu Pei Han Li-Bin Pan Zheng-Wei Zhang Hang Yu Yan Wang Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota Molecules triptolide gut microbiota liver microsome metabolites lc-ms/ms lc/ms<sup>n</sup>-it-tof |
title | Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota |
title_full | Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota |
title_fullStr | Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota |
title_full_unstemmed | Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota |
title_short | Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota |
title_sort | transforming of triptolide into characteristic metabolites by the gut microbiota |
topic | triptolide gut microbiota liver microsome metabolites lc-ms/ms lc/ms<sup>n</sup>-it-tof |
url | https://www.mdpi.com/1420-3049/25/3/606 |
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