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Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase

Background: Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority. Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-...

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Autores principales: Huang, Chong-Yin, Huang, Ya-Jun, Zhang, Zhuo-Yi, Liu, Yi-Song, Liu, Zhao-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187775/
https://www.ncbi.nlm.nih.gov/pubmed/34124222
http://dx.doi.org/10.3389/fvets.2021.659771
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author Huang, Chong-Yin
Huang, Ya-Jun
Zhang, Zhuo-Yi
Liu, Yi-Song
Liu, Zhao-Ying
author_facet Huang, Chong-Yin
Huang, Ya-Jun
Zhang, Zhuo-Yi
Liu, Yi-Song
Liu, Zhao-Ying
author_sort Huang, Chong-Yin
collection PubMed
description Background: Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority. Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined. Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activity Conclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats.
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spelling pubmed-81877752021-06-10 Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase Huang, Chong-Yin Huang, Ya-Jun Zhang, Zhuo-Yi Liu, Yi-Song Liu, Zhao-Ying Front Vet Sci Veterinary Science Background: Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority. Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined. Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activity Conclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8187775/ /pubmed/34124222 http://dx.doi.org/10.3389/fvets.2021.659771 Text en Copyright © 2021 Huang, Huang, Zhang, Liu and Liu. https://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 Veterinary Science
Huang, Chong-Yin
Huang, Ya-Jun
Zhang, Zhuo-Yi
Liu, Yi-Song
Liu, Zhao-Ying
Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title_full Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title_fullStr Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title_full_unstemmed Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title_short Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase
title_sort metabolism and tissue distribution of chelerythrine and effects of macleaya cordata extracts on liver nad(p)h quinone oxidoreductase
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187775/
https://www.ncbi.nlm.nih.gov/pubmed/34124222
http://dx.doi.org/10.3389/fvets.2021.659771
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