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Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated th...

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Autores principales: Liao, Wenting, Jin, Qiwen, Liu, Junning, Ruan, Yiling, Li, Xinran, Shen, Yueyue, Zhang, Zhicheng, Wang, Yong, Wu, Shengming, Zhang, Junying, Kang, Lifeng, Wu, Chunyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043081/
https://www.ncbi.nlm.nih.gov/pubmed/33859560
http://dx.doi.org/10.3389/fphar.2021.599180
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author Liao, Wenting
Jin, Qiwen
Liu, Junning
Ruan, Yiling
Li, Xinran
Shen, Yueyue
Zhang, Zhicheng
Wang, Yong
Wu, Shengming
Zhang, Junying
Kang, Lifeng
Wu, Chunyong
author_facet Liao, Wenting
Jin, Qiwen
Liu, Junning
Ruan, Yiling
Li, Xinran
Shen, Yueyue
Zhang, Zhicheng
Wang, Yong
Wu, Shengming
Zhang, Junying
Kang, Lifeng
Wu, Chunyong
author_sort Liao, Wenting
collection PubMed
description Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated the protective effect of MHD against ALF. In the lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced ALF mouse model, the elevated activities of the serum alanine and aspartate transaminases as well as the liver pathological damage were markedly alleviated by MHD. Subsequently, a metabolomics study based on the ultrahigh performance liquid chromatograph coupled with Q Exactive Orbitrap mass spectrometry was carried to clarify the therapeutic mechanisms of MHD against ALF. A total of 36 metabolites contributing to LPS/D-GalN-induced ALF were identified in the serum samples, among which the abnormalities of 27 metabolites were ameliorated by MHD. The analysis of metabolic pathways revealed that the therapeutic effects of MHD are likely due to the modulation of the metabolic disorders of tricarboxylic acid (TCA) cycle, retinol metabolism, tryptophan metabolism, arginine and proline metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan synthesis, as well as cysteine and methionine metabolism. This study demonstrated for the first time that MHD exerted an obvious protective effect against ALF mainly through the regulation of TCA cycle and amino acid metabolism, highlighting the importance of metabolomics to investigate the drug-targeted metabolic pathways.
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spelling pubmed-80430812021-04-14 Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism Liao, Wenting Jin, Qiwen Liu, Junning Ruan, Yiling Li, Xinran Shen, Yueyue Zhang, Zhicheng Wang, Yong Wu, Shengming Zhang, Junying Kang, Lifeng Wu, Chunyong Front Pharmacol Pharmacology Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated the protective effect of MHD against ALF. In the lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced ALF mouse model, the elevated activities of the serum alanine and aspartate transaminases as well as the liver pathological damage were markedly alleviated by MHD. Subsequently, a metabolomics study based on the ultrahigh performance liquid chromatograph coupled with Q Exactive Orbitrap mass spectrometry was carried to clarify the therapeutic mechanisms of MHD against ALF. A total of 36 metabolites contributing to LPS/D-GalN-induced ALF were identified in the serum samples, among which the abnormalities of 27 metabolites were ameliorated by MHD. The analysis of metabolic pathways revealed that the therapeutic effects of MHD are likely due to the modulation of the metabolic disorders of tricarboxylic acid (TCA) cycle, retinol metabolism, tryptophan metabolism, arginine and proline metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan synthesis, as well as cysteine and methionine metabolism. This study demonstrated for the first time that MHD exerted an obvious protective effect against ALF mainly through the regulation of TCA cycle and amino acid metabolism, highlighting the importance of metabolomics to investigate the drug-targeted metabolic pathways. Frontiers Media S.A. 2021-03-29 /pmc/articles/PMC8043081/ /pubmed/33859560 http://dx.doi.org/10.3389/fphar.2021.599180 Text en Copyright © 2021 Liao, Jin, Liu, Ruan, Li, Shen, Zhang, Wang, Wu, Zhang, Kang and Wu. 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
Liao, Wenting
Jin, Qiwen
Liu, Junning
Ruan, Yiling
Li, Xinran
Shen, Yueyue
Zhang, Zhicheng
Wang, Yong
Wu, Shengming
Zhang, Junying
Kang, Lifeng
Wu, Chunyong
Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title_full Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title_fullStr Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title_full_unstemmed Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title_short Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism
title_sort mahuang decoction antagonizes acute liver failure via modulating tricarboxylic acid cycle and amino acids metabolism
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043081/
https://www.ncbi.nlm.nih.gov/pubmed/33859560
http://dx.doi.org/10.3389/fphar.2021.599180
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