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Ganoderic Acid A Metabolites and Their Metabolic Kinetics
Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and u...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339268/ https://www.ncbi.nlm.nih.gov/pubmed/28326038 http://dx.doi.org/10.3389/fphar.2017.00101 |
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author | Cao, Fang-Rui Feng, Li Ye, Lin-Hu Wang, Li-Sha Xiao, Bing-Xin Tao, Xue Chang, Qi |
author_facet | Cao, Fang-Rui Feng, Li Ye, Lin-Hu Wang, Li-Sha Xiao, Bing-Xin Tao, Xue Chang, Qi |
author_sort | Cao, Fang-Rui |
collection | PubMed |
description | Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and urine after intravenous administration to rats (20 mg/kg), and in vitro by incubating with rat liver microsomes (RLMs) and human liver microsomes (HLMs); (2) to investigate the metabolic kinetics of main GAA metabolites. Using HPLC-DAD-MS/MS techniques, a total of 37 metabolites were tentatively characterized from in vivo samples based on their fragmentation behaviors. The metabolites detected in in vitro samples were similar to those found in vivo. GAA underwent extensive phase I and II metabolism. The main metabolic soft spots of GAA were 3, 7, 11, 15, 23-carbonyl groups (or hydroxyl groups) and 12, 20, 28 (29)-carbon atoms. Ganoderic acid C(2) (GAC(2)) and 7β,15-dihydroxy-3,11,23-trioxo-lanost-26-oic acid were two main reduction metabolites of GAA, and their kinetics followed classical hyperbolic kinetics. The specific isoenzyme responsible for the biotransformation of the two metabolites in RLMs and HLMs was CYP3A. This is the first report on the comprehensive metabolism of GAA, as well as the metabolic kinetics of its main metabolites. |
format | Online Article Text |
id | pubmed-5339268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53392682017-03-21 Ganoderic Acid A Metabolites and Their Metabolic Kinetics Cao, Fang-Rui Feng, Li Ye, Lin-Hu Wang, Li-Sha Xiao, Bing-Xin Tao, Xue Chang, Qi Front Pharmacol Pharmacology Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and urine after intravenous administration to rats (20 mg/kg), and in vitro by incubating with rat liver microsomes (RLMs) and human liver microsomes (HLMs); (2) to investigate the metabolic kinetics of main GAA metabolites. Using HPLC-DAD-MS/MS techniques, a total of 37 metabolites were tentatively characterized from in vivo samples based on their fragmentation behaviors. The metabolites detected in in vitro samples were similar to those found in vivo. GAA underwent extensive phase I and II metabolism. The main metabolic soft spots of GAA were 3, 7, 11, 15, 23-carbonyl groups (or hydroxyl groups) and 12, 20, 28 (29)-carbon atoms. Ganoderic acid C(2) (GAC(2)) and 7β,15-dihydroxy-3,11,23-trioxo-lanost-26-oic acid were two main reduction metabolites of GAA, and their kinetics followed classical hyperbolic kinetics. The specific isoenzyme responsible for the biotransformation of the two metabolites in RLMs and HLMs was CYP3A. This is the first report on the comprehensive metabolism of GAA, as well as the metabolic kinetics of its main metabolites. Frontiers Media S.A. 2017-03-07 /pmc/articles/PMC5339268/ /pubmed/28326038 http://dx.doi.org/10.3389/fphar.2017.00101 Text en Copyright © 2017 Cao, Feng, Ye, Wang, Xiao, Tao and Chang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Cao, Fang-Rui Feng, Li Ye, Lin-Hu Wang, Li-Sha Xiao, Bing-Xin Tao, Xue Chang, Qi Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title | Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title_full | Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title_fullStr | Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title_full_unstemmed | Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title_short | Ganoderic Acid A Metabolites and Their Metabolic Kinetics |
title_sort | ganoderic acid a metabolites and their metabolic kinetics |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339268/ https://www.ncbi.nlm.nih.gov/pubmed/28326038 http://dx.doi.org/10.3389/fphar.2017.00101 |
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