Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible o...

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Main Authors: Jing Zhang, Yang Lv, Wen-Jin Shi, Xu-Yan Guo, Jing-Jing Xu, Peng-Pu Wang, Xue-Tai Chen, Lin-Han Xiang, Feng Xu, Xuan Wang, Shao-Qing Cai
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.995641/full
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author Jing Zhang
Yang Lv
Jing Zhang
Wen-Jin Shi
Xu-Yan Guo
Jing-Jing Xu
Peng-Pu Wang
Xue-Tai Chen
Lin-Han Xiang
Feng Xu
Xuan Wang
Shao-Qing Cai
author_facet Jing Zhang
Yang Lv
Jing Zhang
Wen-Jin Shi
Xu-Yan Guo
Jing-Jing Xu
Peng-Pu Wang
Xue-Tai Chen
Lin-Han Xiang
Feng Xu
Xuan Wang
Shao-Qing Cai
author_sort Jing Zhang
collection DOAJ
description Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time.Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn).Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3′-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation.Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.
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spelling doaj.art-2b85bd72a7d04ef3b2350267d310c2d92022-12-22T02:26:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.995641995641Metabolism of Paeoniae Radix Rubra and its 14 constituents in miceJing ZhangYang LvJing ZhangWen-Jin ShiXu-Yan GuoJing-Jing XuPeng-Pu WangXue-Tai ChenLin-Han XiangFeng XuXuan WangShao-Qing CaiObjective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time.Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn).Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3′-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation.Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.https://www.frontiersin.org/articles/10.3389/fphar.2022.995641/fullPaeoniae Radix Rubrapaeoniflorincatechinellagic acidmethylgallatein vivo metabolism
spellingShingle Jing Zhang
Yang Lv
Jing Zhang
Wen-Jin Shi
Xu-Yan Guo
Jing-Jing Xu
Peng-Pu Wang
Xue-Tai Chen
Lin-Han Xiang
Feng Xu
Xuan Wang
Shao-Qing Cai
Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
Frontiers in Pharmacology
Paeoniae Radix Rubra
paeoniflorin
catechin
ellagic acid
methylgallate
in vivo metabolism
title Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
title_full Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
title_fullStr Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
title_full_unstemmed Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
title_short Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice
title_sort metabolism of paeoniae radix rubra and its 14 constituents in mice
topic Paeoniae Radix Rubra
paeoniflorin
catechin
ellagic acid
methylgallate
in vivo metabolism
url https://www.frontiersin.org/articles/10.3389/fphar.2022.995641/full
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