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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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Autores principales: Peng, Ran, Ma, Shu-Rong, Fu, Jie, Han, Pei, Pan, Li-Bin, Zhang, Zheng-Wei, Yu, Hang, Wang, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037371/
https://www.ncbi.nlm.nih.gov/pubmed/32019202
http://dx.doi.org/10.3390/molecules25030606
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author Peng, Ran
Ma, Shu-Rong
Fu, Jie
Han, Pei
Pan, Li-Bin
Zhang, Zheng-Wei
Yu, Hang
Wang, Yan
author_facet Peng, Ran
Ma, Shu-Rong
Fu, Jie
Han, Pei
Pan, Li-Bin
Zhang, Zheng-Wei
Yu, Hang
Wang, Yan
author_sort Peng, Ran
collection PubMed
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(n)-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 pubmed-70373712020-03-11 Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota Peng, Ran Ma, Shu-Rong Fu, Jie Han, Pei Pan, Li-Bin Zhang, Zheng-Wei Yu, Hang Wang, Yan Molecules Article 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(n)-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. MDPI 2020-01-30 /pmc/articles/PMC7037371/ /pubmed/32019202 http://dx.doi.org/10.3390/molecules25030606 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peng, Ran
Ma, Shu-Rong
Fu, Jie
Han, Pei
Pan, Li-Bin
Zhang, Zheng-Wei
Yu, Hang
Wang, Yan
Transforming of Triptolide into Characteristic Metabolites by the Gut Microbiota
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037371/
https://www.ncbi.nlm.nih.gov/pubmed/32019202
http://dx.doi.org/10.3390/molecules25030606
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