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Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice

Alcoholic liver disease (ALD) caused by excessive drinking is a health and economic concern worldwide. Given the high morbidity, mortality, and the progressive nature of ALD, finding effective interventions is essential. Previous studies have confirmed that edible food plants and their bioactive com...

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Autores principales: Guo, Min, Gu, Liwei, Hui, Heping, Li, Xiaodong, Jin, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966672/
https://www.ncbi.nlm.nih.gov/pubmed/35370722
http://dx.doi.org/10.3389/fphar.2022.830532
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author Guo, Min
Gu, Liwei
Hui, Heping
Li, Xiaodong
Jin, Ling
author_facet Guo, Min
Gu, Liwei
Hui, Heping
Li, Xiaodong
Jin, Ling
author_sort Guo, Min
collection PubMed
description Alcoholic liver disease (ALD) caused by excessive drinking is a health and economic concern worldwide. Given the high morbidity, mortality, and the progressive nature of ALD, finding effective interventions is essential. Previous studies have confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. Dracocephalum tanguticum Maxim (DTM) is one of the important traditional Tibetan medicines in China with the effect of clearing away liver heat, used for the treatment of hepatitis. In this study, the DTM chloroform extract (DtM-C), ethyl acetate extract (DtM-E), and n-butanol extract (DtM-B) were obtained by ethanol extraction combined with fractional extraction. Acute ALD was induced in mice given intragastric ethanol. Serum and liver biochemical markers were detected by ELISA. Liver histological observation, Oil Red O, and Masson’s trichrome staining were performed. Liver injury cells were induced by ethanol. The cell vitality was detected by using MTT colorimetry. The expressions of Nrf2, NF-κB, STAT3, AP-1, CREB, HIF-1α, HO-1, NQO-1, GSTA1, IKB2, and Keap1 were detected by real-time polymerase chain reaction (PCR) to elucidate the mechanism of hepatoprotective effect, and the results were verified by using Western blot. The results of serum liver function indicators (ALT, AST, and ADH), serum hepatic lipid indicators (TC, TG, HDL-C, and LDL-C), and lipid peroxidation indicators (ADH, MDA, SOD, CAT, and GSH-Px) in liver tissue and liver histological observation showed that DtM-E could improve liver function, alleviate fatty degeneration, edema, cell necrosis, and liver fibrosis caused by alcohol. DtM-E also increased the vitality of EtOH-induced liver injury cells, upregulated the mRNA expression of Nrf2, HO-1, NQO-1, and GSTA1, while downregulated the expression of Keap-1, p65, and NF-κB. Western blot results were consistent with PCR. The results suggest that DtM-E has a protective effect against ALD in vitro and in vivo, and its mechanism of action may be related to the activation of Nrf2/Keap-1 and inhibition of the P65/NF-κB signaling pathways.
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spelling pubmed-89666722022-03-31 Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice Guo, Min Gu, Liwei Hui, Heping Li, Xiaodong Jin, Ling Front Pharmacol Pharmacology Alcoholic liver disease (ALD) caused by excessive drinking is a health and economic concern worldwide. Given the high morbidity, mortality, and the progressive nature of ALD, finding effective interventions is essential. Previous studies have confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. Dracocephalum tanguticum Maxim (DTM) is one of the important traditional Tibetan medicines in China with the effect of clearing away liver heat, used for the treatment of hepatitis. In this study, the DTM chloroform extract (DtM-C), ethyl acetate extract (DtM-E), and n-butanol extract (DtM-B) were obtained by ethanol extraction combined with fractional extraction. Acute ALD was induced in mice given intragastric ethanol. Serum and liver biochemical markers were detected by ELISA. Liver histological observation, Oil Red O, and Masson’s trichrome staining were performed. Liver injury cells were induced by ethanol. The cell vitality was detected by using MTT colorimetry. The expressions of Nrf2, NF-κB, STAT3, AP-1, CREB, HIF-1α, HO-1, NQO-1, GSTA1, IKB2, and Keap1 were detected by real-time polymerase chain reaction (PCR) to elucidate the mechanism of hepatoprotective effect, and the results were verified by using Western blot. The results of serum liver function indicators (ALT, AST, and ADH), serum hepatic lipid indicators (TC, TG, HDL-C, and LDL-C), and lipid peroxidation indicators (ADH, MDA, SOD, CAT, and GSH-Px) in liver tissue and liver histological observation showed that DtM-E could improve liver function, alleviate fatty degeneration, edema, cell necrosis, and liver fibrosis caused by alcohol. DtM-E also increased the vitality of EtOH-induced liver injury cells, upregulated the mRNA expression of Nrf2, HO-1, NQO-1, and GSTA1, while downregulated the expression of Keap-1, p65, and NF-κB. Western blot results were consistent with PCR. The results suggest that DtM-E has a protective effect against ALD in vitro and in vivo, and its mechanism of action may be related to the activation of Nrf2/Keap-1 and inhibition of the P65/NF-κB signaling pathways. Frontiers Media S.A. 2022-03-16 /pmc/articles/PMC8966672/ /pubmed/35370722 http://dx.doi.org/10.3389/fphar.2022.830532 Text en Copyright © 2022 Guo, Gu, Hui, Li and Jin. 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
Guo, Min
Gu, Liwei
Hui, Heping
Li, Xiaodong
Jin, Ling
Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title_full Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title_fullStr Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title_full_unstemmed Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title_short Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice
title_sort extracts of dracocephalum tanguticum maxim ameliorate acute alcoholic liver disease via regulating transcription factors in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966672/
https://www.ncbi.nlm.nih.gov/pubmed/35370722
http://dx.doi.org/10.3389/fphar.2022.830532
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