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Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS

Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Ca...

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Autores principales: Cheng, Zhongzhe, Zhou, Xing, Du, Zhifeng, Li, Wenyi, Hu, Bingying, Tian, Jingkui, Zhang, Lin, Huang, Jiangeng, Jiang, Hongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321230/
https://www.ncbi.nlm.nih.gov/pubmed/30297638
http://dx.doi.org/10.3390/pharmaceutics10040178
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author Cheng, Zhongzhe
Zhou, Xing
Du, Zhifeng
Li, Wenyi
Hu, Bingying
Tian, Jingkui
Zhang, Lin
Huang, Jiangeng
Jiang, Hongliang
author_facet Cheng, Zhongzhe
Zhou, Xing
Du, Zhifeng
Li, Wenyi
Hu, Bingying
Tian, Jingkui
Zhang, Lin
Huang, Jiangeng
Jiang, Hongliang
author_sort Cheng, Zhongzhe
collection PubMed
description Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse liver microsomes, respectively. Thereafter, their metabolites were identified and characterized after oral administration in mice. As a result, species difference was found in the metabolic stability of LC-B and LC-C. All three compounds of interest were stable in human and rat liver microsomes, but LC-B and LC-C significantly degraded in mouse liver microsomes. The metabolic instability of LC-B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were identified and characterized in mouse biological matrices. LC-B and LC-C mainly underwent deglycosylation and esterolysis, accompanied by dehydration, dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the preclinical metabolism and disposition process of LC-B and LC-C, which provided additional information for better understanding efficacy and safety.
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spelling pubmed-63212302019-01-11 Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS Cheng, Zhongzhe Zhou, Xing Du, Zhifeng Li, Wenyi Hu, Bingying Tian, Jingkui Zhang, Lin Huang, Jiangeng Jiang, Hongliang Pharmaceutics Article Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse liver microsomes, respectively. Thereafter, their metabolites were identified and characterized after oral administration in mice. As a result, species difference was found in the metabolic stability of LC-B and LC-C. All three compounds of interest were stable in human and rat liver microsomes, but LC-B and LC-C significantly degraded in mouse liver microsomes. The metabolic instability of LC-B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were identified and characterized in mouse biological matrices. LC-B and LC-C mainly underwent deglycosylation and esterolysis, accompanied by dehydration, dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the preclinical metabolism and disposition process of LC-B and LC-C, which provided additional information for better understanding efficacy and safety. MDPI 2018-10-08 /pmc/articles/PMC6321230/ /pubmed/30297638 http://dx.doi.org/10.3390/pharmaceutics10040178 Text en © 2018 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
Cheng, Zhongzhe
Zhou, Xing
Du, Zhifeng
Li, Wenyi
Hu, Bingying
Tian, Jingkui
Zhang, Lin
Huang, Jiangeng
Jiang, Hongliang
Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title_full Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title_fullStr Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title_full_unstemmed Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title_short Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS
title_sort metabolic stability and metabolite characterization of capilliposide b and capilliposide c by lc–qtrap–ms/ms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321230/
https://www.ncbi.nlm.nih.gov/pubmed/30297638
http://dx.doi.org/10.3390/pharmaceutics10040178
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