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Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats
Berberine, a well-known alkaloid, has been proved to possess various pharmacological activities. Previous studies demonstrated that berberine could be extensively metabolized and the metabolites also contributed to its therapeutic effects. However, as for berberine’s metabolites, especially phase II...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874128/ https://www.ncbi.nlm.nih.gov/pubmed/33584274 http://dx.doi.org/10.3389/fphar.2020.594852 |
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author | Feng, Xinchi Wang, Kun Cao, Shijie Ding, Liqin Qiu, Feng |
author_facet | Feng, Xinchi Wang, Kun Cao, Shijie Ding, Liqin Qiu, Feng |
author_sort | Feng, Xinchi |
collection | PubMed |
description | Berberine, a well-known alkaloid, has been proved to possess various pharmacological activities. Previous studies demonstrated that berberine could be extensively metabolized and the metabolites also contributed to its therapeutic effects. However, as for berberine’s metabolites, especially phase II metabolites, pharmacokinetics and excretion studies were rarely reported. The objective of this study was to thoroughly investigate the pharmacokinetic and excretion profiles of berberine and its nine metabolites, namely, berberrubine (M1), demethyleneberberine (M2), jatrorrhizine (M3), jatrorrhizine-3-O-β-D-glucuronide (M4), jatrorrhizine-3-O-sulfate (M5), thalfendine-10-O-β-D-glucuronide (M6), berberrubine-9-O-β-D-glucuronide (M7), demethyleneberberine-2-O-sulfate (M8) and demethyleneberberine-2-O-β-D-glucuronide (M9) in rats. An accurate and reliable LC-MS/MS method was developed and validated for the determination of berberine and its nine metabolites in rat biosamples. Pharmacokinetic profiles of berberine and its nine metabolites were obtained after a single intravenous administration (4.0 mg/kg) and oral administration (48.2, 120 or 240 mg/kg) of berberine in rats. For excretion study, rats were intragastrically administered a single dose of 48.2 mg/kg berberine. Our results showed that berberine could be metabolized rapidly and all the nine metabolites could be detected in vivo. The absolute bioavailability of berberine was 0.37 ± 0.11%. As for the AUC(0–48 h) values, phase II metabolites were much higher than those of phase I metabolites, suggesting that phase II metabolites were the major metabolites exist in blood circulation. 18.6% of the berberine was excreted in feces as berberrubine (M1). The total recovery of berberine and its nine metabolites from urine, bile and feces was 41.2%. This is the first systematic study about the pharmacokinetics and excretion of berberine and its nine metabolites, which will be beneficial for both better understanding the clinical effects and further development of berberine. |
format | Online Article Text |
id | pubmed-7874128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78741282021-02-11 Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats Feng, Xinchi Wang, Kun Cao, Shijie Ding, Liqin Qiu, Feng Front Pharmacol Pharmacology Berberine, a well-known alkaloid, has been proved to possess various pharmacological activities. Previous studies demonstrated that berberine could be extensively metabolized and the metabolites also contributed to its therapeutic effects. However, as for berberine’s metabolites, especially phase II metabolites, pharmacokinetics and excretion studies were rarely reported. The objective of this study was to thoroughly investigate the pharmacokinetic and excretion profiles of berberine and its nine metabolites, namely, berberrubine (M1), demethyleneberberine (M2), jatrorrhizine (M3), jatrorrhizine-3-O-β-D-glucuronide (M4), jatrorrhizine-3-O-sulfate (M5), thalfendine-10-O-β-D-glucuronide (M6), berberrubine-9-O-β-D-glucuronide (M7), demethyleneberberine-2-O-sulfate (M8) and demethyleneberberine-2-O-β-D-glucuronide (M9) in rats. An accurate and reliable LC-MS/MS method was developed and validated for the determination of berberine and its nine metabolites in rat biosamples. Pharmacokinetic profiles of berberine and its nine metabolites were obtained after a single intravenous administration (4.0 mg/kg) and oral administration (48.2, 120 or 240 mg/kg) of berberine in rats. For excretion study, rats were intragastrically administered a single dose of 48.2 mg/kg berberine. Our results showed that berberine could be metabolized rapidly and all the nine metabolites could be detected in vivo. The absolute bioavailability of berberine was 0.37 ± 0.11%. As for the AUC(0–48 h) values, phase II metabolites were much higher than those of phase I metabolites, suggesting that phase II metabolites were the major metabolites exist in blood circulation. 18.6% of the berberine was excreted in feces as berberrubine (M1). The total recovery of berberine and its nine metabolites from urine, bile and feces was 41.2%. This is the first systematic study about the pharmacokinetics and excretion of berberine and its nine metabolites, which will be beneficial for both better understanding the clinical effects and further development of berberine. Frontiers Media S.A. 2021-01-15 /pmc/articles/PMC7874128/ /pubmed/33584274 http://dx.doi.org/10.3389/fphar.2020.594852 Text en Copyright © 2021 Feng, Wang, Cao, Ding and Qiu. 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) and the copyright owner(s) 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 Feng, Xinchi Wang, Kun Cao, Shijie Ding, Liqin Qiu, Feng Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title | Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title_full | Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title_fullStr | Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title_full_unstemmed | Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title_short | Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats |
title_sort | pharmacokinetics and excretion of berberine and its nine metabolites in rats |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874128/ https://www.ncbi.nlm.nih.gov/pubmed/33584274 http://dx.doi.org/10.3389/fphar.2020.594852 |
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