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

文献类型：期刊论文

作者Xue, Yaru4,5; Deng, Qiangqiang4; Zhang, Qingli6; Ma, Zhenghua1,2,3; Chen, Binfan4,5; Yu, Xiaolu4,5; Peng, Huige4; Yao, Sheng2,3,4; Liu, Jia6; Ye, Yang1,2,3,4
刊名SCIENTIFIC REPORTS
出版日期2020-12-17
卷号10期号:1页码:13
ISSN号2045-2322
DOI10.1038/s41598-020-79400-0
通讯作者Ye, Yang(yye@simm.ac.cn) ; Pan, Guoyu(gypan@simm.ac.cn)
英文摘要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.
WOS关键词ARACHIDONIC-ACID ; CARBON-TETRACHLORIDE ; 12/15-LIPOXYGENASE ; INHIBITION ; DYSFUNCTION ; 15-HUMAN ; 12-HUMAN ; MODELS ; POTENT ; CELLS
资助项目Chinese Academy of Sciences[XDA16020205] ; National Science Foundation of China[81872927] ; International Partnership Program of Chinese Academy of Sciences[153631KYSB20160004] ; Independent Deployment Program of the Institute of Pharmaceutical Innovation of the Chinese Academy of Sciences[CASIMM0120184005] ; China Postdoctoral Science Foundation[2019M651623]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE RESEARCH
WOS记录号WOS:000603258300074
源URL[http://119.78.100.183/handle/2S10ELR8/296064]  
专题新药研究国家重点实验室
通讯作者Ye, Yang; Pan, Guoyu
作者单位1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Inst Mat Med, State Key Lab Drug Res & Nat Prod, Chem Dept Shanghai, Shanghai 201203, Peoples R China
3.SIMM CUHK Joint Res Lab Promoting Globalizat Trad, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Inst Technol Serv Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Xue, Yaru,Deng, Qiangqiang,Zhang, Qingli,et al. Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway[J]. SCIENTIFIC REPORTS,2020,10(1):13.
APA Xue, Yaru.,Deng, Qiangqiang.,Zhang, Qingli.,Ma, Zhenghua.,Chen, Binfan.,...&Pan, Guoyu.(2020).Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway.SCIENTIFIC REPORTS,10(1),13.
MLA Xue, Yaru,et al."Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway".SCIENTIFIC REPORTS 10.1(2020):13.

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来源：上海药物研究所

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