Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

Abstract Arachidonic acid (AA) signaling pathway is an important constituent of inflammatory processes. In our previous study, it was found that dihydro-stilbene gigantol relieved hepatic inflammation in mice with CCl4-induced acute liver injury. This study aimed to investigate the involvement of ar...

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Autores principales:	Yaru Xue, Qiangqiang Deng, Qingli Zhang, Zhenghua Ma, Binfan Chen, Xiaolu Yu, Huige Peng, Sheng Yao, Jia Liu, Yang Ye, Guoyu Pan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5422c27e8d144a1294213cea143e9bfe
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spelling	oai:doaj.org-article:5422c27e8d144a1294213cea143e9bfe2021-12-02T13:58:14ZGigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway10.1038/s41598-020-79400-02045-2322https://doaj.org/article/5422c27e8d144a1294213cea143e9bfe2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79400-0https://doaj.org/toc/2045-2322Abstract Arachidonic acid (AA) signaling pathway is an important constituent of inflammatory processes. In our previous study, it was found that dihydro-stilbene gigantol relieved hepatic inflammation in mice with CCl4-induced acute liver injury. This study aimed to investigate the involvement of arachidonate metabolic cascade in this process. Our results showed CCl4 activated AA metabolism with the evidence of cPLA2 phosphorylation, which was dependent on the MAPK/JNK activation. Pretreatment with JNK inhibitor SU3327 or gigantol abolished the cPLA2 activation, along with the attenuation of liver damage. Besides, gigantol markedly decreased immune cells activation. Metabolomic analysis revealed that gigantol universally reversed the upregulation of major AA metabolites in injured mouse livers induced by CCl4, especially 12-hydroxyeicosatetraenoic acid (12-HETE). Gigantol also decreased the mRNA and protein expression of platelet-, and leukocyte-type 12-lipoxxygenase (LOX) in the liver. Furthermore, pan-LOX inhibitor nordihydroguaiaretic acid (NDGA) and specific 12-LOX inhibitors baicalein and ML351 attenuated the liver injury to the same extent as gigantol. Overall, our study elucidated a comprehensive profile of AA metabolites during hepatic inflammation caused by CCl4, highlighting the role of 12-LOX-12-HETE pathway in this process. And gigantol alleviated liver inflammation partly through inhibiting the JNK/cPLA2/12-LOX pathway.Yaru XueQiangqiang DengQingli ZhangZhenghua MaBinfan ChenXiaolu YuHuige PengSheng YaoJia LiuYang YeGuoyu PanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yaru Xue Qiangqiang Deng Qingli Zhang Zhenghua Ma Binfan Chen Xiaolu Yu Huige Peng Sheng Yao Jia Liu Yang Ye Guoyu Pan Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
description	Abstract Arachidonic acid (AA) signaling pathway is an important constituent of inflammatory processes. In our previous study, it was found that dihydro-stilbene gigantol relieved hepatic inflammation in mice with CCl4-induced acute liver injury. This study aimed to investigate the involvement of arachidonate metabolic cascade in this process. Our results showed CCl4 activated AA metabolism with the evidence of cPLA2 phosphorylation, which was dependent on the MAPK/JNK activation. Pretreatment with JNK inhibitor SU3327 or gigantol abolished the cPLA2 activation, along with the attenuation of liver damage. Besides, gigantol markedly decreased immune cells activation. Metabolomic analysis revealed that gigantol universally reversed the upregulation of major AA metabolites in injured mouse livers induced by CCl4, especially 12-hydroxyeicosatetraenoic acid (12-HETE). Gigantol also decreased the mRNA and protein expression of platelet-, and leukocyte-type 12-lipoxxygenase (LOX) in the liver. Furthermore, pan-LOX inhibitor nordihydroguaiaretic acid (NDGA) and specific 12-LOX inhibitors baicalein and ML351 attenuated the liver injury to the same extent as gigantol. Overall, our study elucidated a comprehensive profile of AA metabolites during hepatic inflammation caused by CCl4, highlighting the role of 12-LOX-12-HETE pathway in this process. And gigantol alleviated liver inflammation partly through inhibiting the JNK/cPLA2/12-LOX pathway.
format	article
author	Yaru Xue Qiangqiang Deng Qingli Zhang Zhenghua Ma Binfan Chen Xiaolu Yu Huige Peng Sheng Yao Jia Liu Yang Ye Guoyu Pan
author_facet	Yaru Xue Qiangqiang Deng Qingli Zhang Zhenghua Ma Binfan Chen Xiaolu Yu Huige Peng Sheng Yao Jia Liu Yang Ye Guoyu Pan
author_sort	Yaru Xue
title	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
title_short	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
title_full	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
title_fullStr	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
title_full_unstemmed	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
title_sort	gigantol ameliorates ccl4-induced liver injury via preventing activation of jnk/cpla2/12-lox inflammatory pathway
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5422c27e8d144a1294213cea143e9bfe
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Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

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