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Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present...

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Autores principales: Qu, Jialin, Chen, Qiuyue, Wei, Tianfu, Dou, Ning, Shang, Dong, Yuan, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468746/
https://www.ncbi.nlm.nih.gov/pubmed/36110520
http://dx.doi.org/10.3389/fphar.2022.915535
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author Qu, Jialin
Chen, Qiuyue
Wei, Tianfu
Dou, Ning
Shang, Dong
Yuan, Dan
author_facet Qu, Jialin
Chen, Qiuyue
Wei, Tianfu
Dou, Ning
Shang, Dong
Yuan, Dan
author_sort Qu, Jialin
collection PubMed
description Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound–target–pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4′-sulfate, tectoridin-4′-sulfate, and 6″-O-xylosyltectoridin-4′-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.
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spelling pubmed-94687462022-09-14 Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model Qu, Jialin Chen, Qiuyue Wei, Tianfu Dou, Ning Shang, Dong Yuan, Dan Front Pharmacol Pharmacology Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound–target–pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4′-sulfate, tectoridin-4′-sulfate, and 6″-O-xylosyltectoridin-4′-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9468746/ /pubmed/36110520 http://dx.doi.org/10.3389/fphar.2022.915535 Text en Copyright © 2022 Qu, Chen, Wei, Dou, Shang and Yuan. 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 Pharmacology
Qu, Jialin
Chen, Qiuyue
Wei, Tianfu
Dou, Ning
Shang, Dong
Yuan, Dan
Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title_full Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title_fullStr Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title_full_unstemmed Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title_short Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
title_sort systematic characterization of puerariae flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468746/
https://www.ncbi.nlm.nih.gov/pubmed/36110520
http://dx.doi.org/10.3389/fphar.2022.915535
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