In vitro Metabolism of Humantenine in Liver Microsomes from Human, Pig, Goat and Rat.
Gelsemium
HPLC/QqTOF-MS
Metabolism
comparative
humantenine
liver microsome.
Journal
Current drug metabolism
ISSN: 1875-5453
Titre abrégé: Curr Drug Metab
Pays: Netherlands
ID NLM: 100960533
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
01
2021
revised:
11
06
2021
accepted:
16
06
2021
pubmed:
2
9
2021
medline:
1
3
2022
entrez:
1
9
2021
Statut:
ppublish
Résumé
Gelsemium elegans Benth (G. elegans) is a well-known toxic plant. Alkaloids are the main active components of G. elegans. Currently, the metabolism of several alkaloids, such as gelsenicine, koumine, and gelsemine, has been widely studied. However, as one of the most important alkaloids in G. elegans, the metabolism of humantenine has not been studied yet. In order to elaborate on the in vitro metabolism of humantenine, a comparative analysis of its metabolic profile in human, pig, goat and rat liver microsomes was carried out using high performance chromatography/ quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) for the first time. Totally, ten metabolites of humantenine were identified in liver microsomes from human (HLMs), pig (PLMs), goat (GLMs) and rat (RLMs) based on the accurate MS/MS spectra. Five metabolic pathways of humantenine, including demethylation, dehydrogenation, oxidation, dehydrogenation and oxidation, and demethylation and oxidation, were proposed in this study. There were qualitative and quantitative species differences in the metabolism of humantenine among the four species. The in vitro metabolism of humantenine in HLMs, PLMs, GLMs and RLMs was studied by a sensitive and specific detection method based on HPLC/QqTOF-MS. The results indicated that there were species-related differences in the metabolism of humantenine. This work might be of great significance for the further research and explanation of species differences in terms of toxicological effects of G. elegans.
Sections du résumé
BACKGROUND
BACKGROUND
Gelsemium elegans Benth (G. elegans) is a well-known toxic plant. Alkaloids are the main active components of G. elegans. Currently, the metabolism of several alkaloids, such as gelsenicine, koumine, and gelsemine, has been widely studied. However, as one of the most important alkaloids in G. elegans, the metabolism of humantenine has not been studied yet.
METHODS
METHODS
In order to elaborate on the in vitro metabolism of humantenine, a comparative analysis of its metabolic profile in human, pig, goat and rat liver microsomes was carried out using high performance chromatography/ quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) for the first time.
RESULTS
RESULTS
Totally, ten metabolites of humantenine were identified in liver microsomes from human (HLMs), pig (PLMs), goat (GLMs) and rat (RLMs) based on the accurate MS/MS spectra. Five metabolic pathways of humantenine, including demethylation, dehydrogenation, oxidation, dehydrogenation and oxidation, and demethylation and oxidation, were proposed in this study. There were qualitative and quantitative species differences in the metabolism of humantenine among the four species.
CONCLUSION
CONCLUSIONS
The in vitro metabolism of humantenine in HLMs, PLMs, GLMs and RLMs was studied by a sensitive and specific detection method based on HPLC/QqTOF-MS. The results indicated that there were species-related differences in the metabolism of humantenine. This work might be of great significance for the further research and explanation of species differences in terms of toxicological effects of G. elegans.
Identifiants
pubmed: 34468296
pii: CDM-EPUB-117600
doi: 10.2174/1389200222666210901113530
doi:
Substances chimiques
Alkaloids
0
humantenine
82375-29-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
795-7801Subventions
Organisme : National Key R&D Program of Intergovernmental Key Projects of China
ID : 2018YFE0101700
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.