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Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and...

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Autores principales: Cao, Liping, Li, Zhenghong, Ren, Yi, Wang, Mengmeng, Yang, Zhizhou, Zhang, Wei, Han, Xiaoqin, Yao, Mengya, Sun, Zhaorui, Nie, Shinan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120308/
https://www.ncbi.nlm.nih.gov/pubmed/33995024
http://dx.doi.org/10.3389/fphar.2021.627716
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author Cao, Liping
Li, Zhenghong
Ren, Yi
Wang, Mengmeng
Yang, Zhizhou
Zhang, Wei
Han, Xiaoqin
Yao, Mengya
Sun, Zhaorui
Nie, Shinan
author_facet Cao, Liping
Li, Zhenghong
Ren, Yi
Wang, Mengmeng
Yang, Zhizhou
Zhang, Wei
Han, Xiaoqin
Yao, Mengya
Sun, Zhaorui
Nie, Shinan
author_sort Cao, Liping
collection PubMed
description Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.
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spelling pubmed-81203082021-05-15 Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway Cao, Liping Li, Zhenghong Ren, Yi Wang, Mengmeng Yang, Zhizhou Zhang, Wei Han, Xiaoqin Yao, Mengya Sun, Zhaorui Nie, Shinan Front Pharmacol Pharmacology Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8120308/ /pubmed/33995024 http://dx.doi.org/10.3389/fphar.2021.627716 Text en Copyright © 2021 Cao, Li, Ren, Wang, Yang, Zhang, Han, Yao, Sun and Nie. 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
Cao, Liping
Li, Zhenghong
Ren, Yi
Wang, Mengmeng
Yang, Zhizhou
Zhang, Wei
Han, Xiaoqin
Yao, Mengya
Sun, Zhaorui
Nie, Shinan
Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title_full Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title_fullStr Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title_full_unstemmed Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title_short Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway
title_sort xuebijing protects against septic acute liver injury based on regulation of gsk-3β pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120308/
https://www.ncbi.nlm.nih.gov/pubmed/33995024
http://dx.doi.org/10.3389/fphar.2021.627716
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