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

doi:10.1038/s41598-020-79400-0

	Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway
	Xue, Yaru 1,2; Deng, Qiangqiang 1; Zhang, Qingli 3; Ma, Zhenghua4,5,6 ; Chen, Binfan 1,2; Yu, Xiaolu 1,2; Peng, Huige 1; Yao, Sheng 1,4,5; Liu, Jia 3; Ye, Yang1,4,5,6 ; Pan, Guoyu 1,2
	2020-12-17
发表期刊	SCIENTIFIC REPORTS (IF:3.8[JCR-2023],4.3[5-Year])
ISSN	2045-2322
卷号	10 期号:1
发表状态	已发表
DOI	10.1038/s41598-020-79400-0
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.
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
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
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000603258300074
出版者	NATURE RESEARCH
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125046
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_叶阳组生命科学与技术学院_博士生
通讯作者	Ye, Yang; Pan, Guoyu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Inst Technol Serv Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Inst Mat Med, State Key Lab Drug Res & Nat Prod, Chem Dept Shanghai, Shanghai 201203, Peoples R China; 5.SIMM CUHK Joint Res Lab Promoting Globalizat Trad, Shanghai 201203, Peoples R China; 6.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
通讯作者单位	生命科学与技术学院
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).
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).
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).