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Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats

Cholestasis is the most destructive pathological manifestation of liver disease and available treatments are very limited. Paeoniae Radix Rubra (PRR) is an important traditional Chinese drug used to treat cholestasis. This study combined targeted metabonomics, PCR array analysis, and 16S rRNA sequen...

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Autores principales: Xu, Jing-Jing, Xu, Feng, Wang, Wei, Wang, Peng-Pu, Xian, Jing, Han, Xing, Shang, Ming-Ying, Liu, Guang-Xue, Wang, Xuan, Cai, Shao-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633937/
https://www.ncbi.nlm.nih.gov/pubmed/36339580
http://dx.doi.org/10.3389/fphar.2022.1002922
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author Xu, Jing-Jing
Xu, Feng
Wang, Wei
Wang, Peng-Pu
Xian, Jing
Han, Xing
Shang, Ming-Ying
Liu, Guang-Xue
Wang, Xuan
Cai, Shao-Qing
author_facet Xu, Jing-Jing
Xu, Feng
Wang, Wei
Wang, Peng-Pu
Xian, Jing
Han, Xing
Shang, Ming-Ying
Liu, Guang-Xue
Wang, Xuan
Cai, Shao-Qing
author_sort Xu, Jing-Jing
collection PubMed
description Cholestasis is the most destructive pathological manifestation of liver disease and available treatments are very limited. Paeoniae Radix Rubra (PRR) is an important traditional Chinese drug used to treat cholestasis. This study combined targeted metabonomics, PCR array analysis, and 16S rRNA sequencing analysis to further clarify the mechanisms of PRR in the treatment of cholestasis. PRR conspicuously reversed the elevation of fatty acids (FFA 14:0 and other 14 fatty acids) and the decrease of organic acids (pyruvic acid and citric acid) in a cholestatic model induced by α-naphthyl isothiocyanate (ANIT). Eight elevated amino acids (L-proline, etc.) and five elevated secondary bile acids (taurohyodeoxycholic acid, etc.) in model rats were also reduced by PRR. Pathway analysis revealed that PRR significantly alleviated eight pathways (β-alanine metabolism). Furthermore, we found that PRR significantly reversed the decrease of Cpt1a, Hadha, Ppara, and Slc25a20 (four genes relevant to fatty acid β-oxidation) mRNAs caused by ANIT, and PRR conspicuously decreased nine acylcarnitines (the forms of fatty acids into mitochondria for β-oxidation) that increased in model rats. These results indicate that PRR could enhance fatty acid β-oxidation, which may be the way for PRR to reduce the levels of 15 fatty acids in the serum of model rats. 16S rRNA sequencing analysis revealed that PRR alleviated gut microbiota disorders in model rats, including upregulating four genera (Coprococcus, Lactobacillus, etc.) and downregulating four genera (Bacteroides, Escherichia, etc.). As the relative abundance of these eight genera was significantly correlated with the levels of the five secondary bile acids (deoxycholic acid, taurolithocholic acid, etc.) reduced by PRR, and Bacteroides and Escherichia were reported to promote the production of secondary bile acid, we inferred that the downregulation of PRR on five secondary bile acids in model rats was inseparable from gut microbiota. Thus, the gut microbiota also might be a potential pharmacological target for the anticholestatic activity of PRR. In conclusion, we consider that the mechanisms of PRR in treating cholestasis include enhancing fatty acid β-oxidation and alleviating gut microbiota disorders.
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spelling pubmed-96339372022-11-05 Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats Xu, Jing-Jing Xu, Feng Wang, Wei Wang, Peng-Pu Xian, Jing Han, Xing Shang, Ming-Ying Liu, Guang-Xue Wang, Xuan Cai, Shao-Qing Front Pharmacol Pharmacology Cholestasis is the most destructive pathological manifestation of liver disease and available treatments are very limited. Paeoniae Radix Rubra (PRR) is an important traditional Chinese drug used to treat cholestasis. This study combined targeted metabonomics, PCR array analysis, and 16S rRNA sequencing analysis to further clarify the mechanisms of PRR in the treatment of cholestasis. PRR conspicuously reversed the elevation of fatty acids (FFA 14:0 and other 14 fatty acids) and the decrease of organic acids (pyruvic acid and citric acid) in a cholestatic model induced by α-naphthyl isothiocyanate (ANIT). Eight elevated amino acids (L-proline, etc.) and five elevated secondary bile acids (taurohyodeoxycholic acid, etc.) in model rats were also reduced by PRR. Pathway analysis revealed that PRR significantly alleviated eight pathways (β-alanine metabolism). Furthermore, we found that PRR significantly reversed the decrease of Cpt1a, Hadha, Ppara, and Slc25a20 (four genes relevant to fatty acid β-oxidation) mRNAs caused by ANIT, and PRR conspicuously decreased nine acylcarnitines (the forms of fatty acids into mitochondria for β-oxidation) that increased in model rats. These results indicate that PRR could enhance fatty acid β-oxidation, which may be the way for PRR to reduce the levels of 15 fatty acids in the serum of model rats. 16S rRNA sequencing analysis revealed that PRR alleviated gut microbiota disorders in model rats, including upregulating four genera (Coprococcus, Lactobacillus, etc.) and downregulating four genera (Bacteroides, Escherichia, etc.). As the relative abundance of these eight genera was significantly correlated with the levels of the five secondary bile acids (deoxycholic acid, taurolithocholic acid, etc.) reduced by PRR, and Bacteroides and Escherichia were reported to promote the production of secondary bile acid, we inferred that the downregulation of PRR on five secondary bile acids in model rats was inseparable from gut microbiota. Thus, the gut microbiota also might be a potential pharmacological target for the anticholestatic activity of PRR. In conclusion, we consider that the mechanisms of PRR in treating cholestasis include enhancing fatty acid β-oxidation and alleviating gut microbiota disorders. Frontiers Media S.A. 2022-10-21 /pmc/articles/PMC9633937/ /pubmed/36339580 http://dx.doi.org/10.3389/fphar.2022.1002922 Text en Copyright © 2022 Xu, Xu, Wang, Wang, Xian, Han, Shang, Liu, Wang and Cai. 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
Xu, Jing-Jing
Xu, Feng
Wang, Wei
Wang, Peng-Pu
Xian, Jing
Han, Xing
Shang, Ming-Ying
Liu, Guang-Xue
Wang, Xuan
Cai, Shao-Qing
Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title_full Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title_fullStr Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title_full_unstemmed Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title_short Paeoniae Radix Rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
title_sort paeoniae radix rubra can enhance fatty acid β-oxidation and alleviate gut microbiota disorder in α-naphthyl isothiocyanate induced cholestatic model rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633937/
https://www.ncbi.nlm.nih.gov/pubmed/36339580
http://dx.doi.org/10.3389/fphar.2022.1002922
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