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Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3

Endoplasmic reticulum stress (ERS) plays a key role in alcohol liver injury (ALI). Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a potential modifier of ERS. It was examined whether the protective effect of Qinggan Huoxue Recipe (QGHXR) against ALI was associated with LPCAT3 by suppressing E...

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Autores principales: Lu, Yifei, Shao, Mingmei, Xiang, Hongjiao, Wang, Junmin, Ji, Guang, Wu, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009225/
https://www.ncbi.nlm.nih.gov/pubmed/35431945
http://dx.doi.org/10.3389/fphar.2022.824185
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author Lu, Yifei
Shao, Mingmei
Xiang, Hongjiao
Wang, Junmin
Ji, Guang
Wu, Tao
author_facet Lu, Yifei
Shao, Mingmei
Xiang, Hongjiao
Wang, Junmin
Ji, Guang
Wu, Tao
author_sort Lu, Yifei
collection PubMed
description Endoplasmic reticulum stress (ERS) plays a key role in alcohol liver injury (ALI). Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a potential modifier of ERS. It was examined whether the protective effect of Qinggan Huoxue Recipe (QGHXR) against ALI was associated with LPCAT3 by suppressing ERS from in vivo and in vitro experiment. Male C57BL/6 mice were randomly divided into five groups (n = 10, each) and treated for 8 weeks as follows: the control diet-fed group (pair-fed), ethanol diet-fed group (EtOH-fed), QGHXR group (EtOH-fed + QGHXR), Qinggan recipe group (EtOH-fed + QGR), and Huoxue recipe group (EtOH-fed + HXR). QGHXR, QGR, and HXR groups attenuated liver injury mainly manifested in reducing serum ALT, AST, and liver TG and reducing the severity of liver cell necrosis and steatosis in ALI mouse models. QGHXR mainly inhibited the mRNA levels of Lxrα, Perk, Eif2α, and Atf4 and activated the mRNA levels of Lpcat3 and Ire1α, while inhibiting the protein levels of LPCAT3, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78 to improve ALI. QGR was more inclined to improve ALI by inhibiting the mRNA levels of Lxrα, Perk, Eif2α, Atif4, and Chop and activating the mRNA levels of Lpcat3 and Ire1α while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u. HXR was more inclined to improve ALI by inhibiting the mRNA levels of Perk, Eif2α, Atf4, and Chop mRNA while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78. Ethanol (100 mM) was used to intervene HepG2 and AML12 to establish an ALI cell model and treated by QGHXR-, QGR-, and HXR-medicated serum (100 mg/L). QGHXR, QGR, and HXR groups mainly reduced the serum TG level and the expression of inflammatory factors such as IL-6 and TNF-α in the liver induced by ethanol. In AML12 cells, QGHXR and its disassembly mainly activated Grp78 mRNA expression together with inhibiting Lxrα, Lpcat3, Eif2α, Atf4, and Xbp1 mRNA expression. The protein expression of eIF2α and XBP1u was inhibited, and the expression of PERK and GRP78 was activated to alleviate ALI. In HepG2 cells, QGHXR mainly alleviated ALI by inhibiting the mRNA expression of LPCAT3, CHOP, IRE1α, XBP1, eIF2α, CHOP, and IRE1α protein. QGR was more inclined to inhibit the protein expression of PERK, and HXR was more likely to inhibit the protein expression of ATF4.
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spelling pubmed-90092252022-04-15 Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3 Lu, Yifei Shao, Mingmei Xiang, Hongjiao Wang, Junmin Ji, Guang Wu, Tao Front Pharmacol Pharmacology Endoplasmic reticulum stress (ERS) plays a key role in alcohol liver injury (ALI). Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a potential modifier of ERS. It was examined whether the protective effect of Qinggan Huoxue Recipe (QGHXR) against ALI was associated with LPCAT3 by suppressing ERS from in vivo and in vitro experiment. Male C57BL/6 mice were randomly divided into five groups (n = 10, each) and treated for 8 weeks as follows: the control diet-fed group (pair-fed), ethanol diet-fed group (EtOH-fed), QGHXR group (EtOH-fed + QGHXR), Qinggan recipe group (EtOH-fed + QGR), and Huoxue recipe group (EtOH-fed + HXR). QGHXR, QGR, and HXR groups attenuated liver injury mainly manifested in reducing serum ALT, AST, and liver TG and reducing the severity of liver cell necrosis and steatosis in ALI mouse models. QGHXR mainly inhibited the mRNA levels of Lxrα, Perk, Eif2α, and Atf4 and activated the mRNA levels of Lpcat3 and Ire1α, while inhibiting the protein levels of LPCAT3, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78 to improve ALI. QGR was more inclined to improve ALI by inhibiting the mRNA levels of Lxrα, Perk, Eif2α, Atif4, and Chop and activating the mRNA levels of Lpcat3 and Ire1α while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u. HXR was more inclined to improve ALI by inhibiting the mRNA levels of Perk, Eif2α, Atf4, and Chop mRNA while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78. Ethanol (100 mM) was used to intervene HepG2 and AML12 to establish an ALI cell model and treated by QGHXR-, QGR-, and HXR-medicated serum (100 mg/L). QGHXR, QGR, and HXR groups mainly reduced the serum TG level and the expression of inflammatory factors such as IL-6 and TNF-α in the liver induced by ethanol. In AML12 cells, QGHXR and its disassembly mainly activated Grp78 mRNA expression together with inhibiting Lxrα, Lpcat3, Eif2α, Atf4, and Xbp1 mRNA expression. The protein expression of eIF2α and XBP1u was inhibited, and the expression of PERK and GRP78 was activated to alleviate ALI. In HepG2 cells, QGHXR mainly alleviated ALI by inhibiting the mRNA expression of LPCAT3, CHOP, IRE1α, XBP1, eIF2α, CHOP, and IRE1α protein. QGR was more inclined to inhibit the protein expression of PERK, and HXR was more likely to inhibit the protein expression of ATF4. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9009225/ /pubmed/35431945 http://dx.doi.org/10.3389/fphar.2022.824185 Text en Copyright © 2022 Lu, Shao, Xiang, Wang, Ji 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
Lu, Yifei
Shao, Mingmei
Xiang, Hongjiao
Wang, Junmin
Ji, Guang
Wu, Tao
Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title_full Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title_fullStr Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title_full_unstemmed Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title_short Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
title_sort qinggan huoxue recipe alleviates alcoholic liver injury by suppressing endoplasmic reticulum stress through lxr-lpcat3
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009225/
https://www.ncbi.nlm.nih.gov/pubmed/35431945
http://dx.doi.org/10.3389/fphar.2022.824185
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