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Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress
Tripterygium glycoside tablet (TGT), as a common clinical drug, can easily cause liver damage due to the narrow therapeutic window. Glycyrrhizic acid (GA) has a hepatoprotective effect, but the characteristics and mechanism of GA’s impact on TGT-induced acute liver injury by regulating oxidative str...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694034/ https://www.ncbi.nlm.nih.gov/pubmed/36422270 http://dx.doi.org/10.3390/metabo12111128 |
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author | Wang, Qixin Huang, Yuwen Li, Yu Zhang, Luyun Tang, Huan Zhang, Junzhe Cheng, Guangqing Zhao, Minghong Lu, Tianming Zhang, Qian Luo, Piao Zhu, Yinhua Xia, Fei Zhang, Ying Liu, Dandan Wang, Chen Li, Haiyan Qiu, Chong Wang, Jigang Guo, Qiuyan |
author_facet | Wang, Qixin Huang, Yuwen Li, Yu Zhang, Luyun Tang, Huan Zhang, Junzhe Cheng, Guangqing Zhao, Minghong Lu, Tianming Zhang, Qian Luo, Piao Zhu, Yinhua Xia, Fei Zhang, Ying Liu, Dandan Wang, Chen Li, Haiyan Qiu, Chong Wang, Jigang Guo, Qiuyan |
author_sort | Wang, Qixin |
collection | PubMed |
description | Tripterygium glycoside tablet (TGT), as a common clinical drug, can easily cause liver damage due to the narrow therapeutic window. Glycyrrhizic acid (GA) has a hepatoprotective effect, but the characteristics and mechanism of GA’s impact on TGT-induced acute liver injury by regulating oxidative stress remain unelucidated. In this study, TGT-induced acute liver injury models were established in vitro and in vivo. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were quantified. The anti-apoptotic effect of GA was tested using flow cytometry. Potential target proteins of GA were profiled via activity-based protein profiling (ABPP) using a cysteine-specific (IAA-yne) probe. The results demonstrate that GA markedly decreased the concentrations of ALT, AST, AKP, MDA, LDH, TNF-α, IL-1β and IL-6, whereas those of SOD, GSH and CAT increased. GA could inhibit TGT-induced apoptosis in BRL-3A cells. GA bound directly to the cysteine residue of PKM2. The CETSA and enzyme activity results validate the specific targets identified. GA could mitigate TGT-induced acute liver injury by mediating PKM2, reducing oxidative stress and inflammation and reducing hepatocyte apoptosis. |
format | Online Article Text |
id | pubmed-9694034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96940342022-11-26 Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress Wang, Qixin Huang, Yuwen Li, Yu Zhang, Luyun Tang, Huan Zhang, Junzhe Cheng, Guangqing Zhao, Minghong Lu, Tianming Zhang, Qian Luo, Piao Zhu, Yinhua Xia, Fei Zhang, Ying Liu, Dandan Wang, Chen Li, Haiyan Qiu, Chong Wang, Jigang Guo, Qiuyan Metabolites Article Tripterygium glycoside tablet (TGT), as a common clinical drug, can easily cause liver damage due to the narrow therapeutic window. Glycyrrhizic acid (GA) has a hepatoprotective effect, but the characteristics and mechanism of GA’s impact on TGT-induced acute liver injury by regulating oxidative stress remain unelucidated. In this study, TGT-induced acute liver injury models were established in vitro and in vivo. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were quantified. The anti-apoptotic effect of GA was tested using flow cytometry. Potential target proteins of GA were profiled via activity-based protein profiling (ABPP) using a cysteine-specific (IAA-yne) probe. The results demonstrate that GA markedly decreased the concentrations of ALT, AST, AKP, MDA, LDH, TNF-α, IL-1β and IL-6, whereas those of SOD, GSH and CAT increased. GA could inhibit TGT-induced apoptosis in BRL-3A cells. GA bound directly to the cysteine residue of PKM2. The CETSA and enzyme activity results validate the specific targets identified. GA could mitigate TGT-induced acute liver injury by mediating PKM2, reducing oxidative stress and inflammation and reducing hepatocyte apoptosis. MDPI 2022-11-17 /pmc/articles/PMC9694034/ /pubmed/36422270 http://dx.doi.org/10.3390/metabo12111128 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Qixin Huang, Yuwen Li, Yu Zhang, Luyun Tang, Huan Zhang, Junzhe Cheng, Guangqing Zhao, Minghong Lu, Tianming Zhang, Qian Luo, Piao Zhu, Yinhua Xia, Fei Zhang, Ying Liu, Dandan Wang, Chen Li, Haiyan Qiu, Chong Wang, Jigang Guo, Qiuyan Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title | Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title_full | Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title_fullStr | Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title_full_unstemmed | Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title_short | Glycyrrhizic Acid Mitigates Tripterygium-Glycoside-Tablet-Induced Acute Liver Injury via PKM2 Regulated Oxidative Stress |
title_sort | glycyrrhizic acid mitigates tripterygium-glycoside-tablet-induced acute liver injury via pkm2 regulated oxidative stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694034/ https://www.ncbi.nlm.nih.gov/pubmed/36422270 http://dx.doi.org/10.3390/metabo12111128 |
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