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The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis

Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective...

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Autores principales: Wu, Ke-Jia, Liu, Pin-Pin, Chen, Meng-Yuan, Zhou, Meng-Xin, Liu, Xin, Yang, Qing, Xu, Lin, Gong, Zhiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301321/
https://www.ncbi.nlm.nih.gov/pubmed/35873419
http://dx.doi.org/10.3389/fnut.2022.904557
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author Wu, Ke-Jia
Liu, Pin-Pin
Chen, Meng-Yuan
Zhou, Meng-Xin
Liu, Xin
Yang, Qing
Xu, Lin
Gong, Zhiyong
author_facet Wu, Ke-Jia
Liu, Pin-Pin
Chen, Meng-Yuan
Zhou, Meng-Xin
Liu, Xin
Yang, Qing
Xu, Lin
Gong, Zhiyong
author_sort Wu, Ke-Jia
collection PubMed
description Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.
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spelling pubmed-93013212022-07-22 The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis Wu, Ke-Jia Liu, Pin-Pin Chen, Meng-Yuan Zhou, Meng-Xin Liu, Xin Yang, Qing Xu, Lin Gong, Zhiyong Front Nutr Nutrition Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9301321/ /pubmed/35873419 http://dx.doi.org/10.3389/fnut.2022.904557 Text en Copyright © 2022 Wu, Liu, Chen, Zhou, Liu, Yang, Xu and Gong. 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 Nutrition
Wu, Ke-Jia
Liu, Pin-Pin
Chen, Meng-Yuan
Zhou, Meng-Xin
Liu, Xin
Yang, Qing
Xu, Lin
Gong, Zhiyong
The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title_full The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title_fullStr The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title_full_unstemmed The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title_short The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis
title_sort hepatoprotective effect of leonurine hydrochloride against alcoholic liver disease based on transcriptomic and metabolomic analysis
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301321/
https://www.ncbi.nlm.nih.gov/pubmed/35873419
http://dx.doi.org/10.3389/fnut.2022.904557
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