Dihydro-stilbene gigantol relieves CCl4-induced hepatic oxidative stress and inflammation in mice via inhibiting C5b-9 formation in the liver
2020-11
发表期刊ACTA PHARMACOLOGICA SINICA (IF:6.9[JCR-2023],7.6[5-Year])
ISSN1671-4083
EISSN1745-7254
发表状态已发表
DOI10.1038/s41401-020-0406-6
摘要

In general, anti-inflammatory treatment is considered for multiple liver diseases despite the etiology. But current drugs for alleviating liver inflammation have defects, making it necessary to develop more potent and safer drugs for liver injury. In this study, we screened a series of (dihydro-)stilbene or (dihydro-)phenanthrene derivatives extracted from Pholidota chinensis for their potential biological activities. Among 31 compounds, the dihydro-stilbene gigantol exerted most potent protective effects on human hepatocytes against lithocholic acid toxicity, and exhibited solid antioxidative and anti-inflammatory effect in vitro. In mice with CCl4-induced acute liver injury, pre-administration of gigantol (10, 20, 40 mg center dot kg(-1)center dot d(-1), po, for 7 days) dose-dependently decreased serum transaminase levels and improved pathological changes in liver tissues. The elevated lipid peroxidation and inflammatory responses in the livers were also significantly alleviated by gigantol. The pharmacokinetic studies showed that gigantol was highly concentrated in the mouse livers, which consisted with its efficacy in preventing liver injury. Using a label-free quantitative proteomic analysis we revealed that gigantol mainly regulated the immune system process in liver tissues of CCl4-treated mice, and the complement and coagulation cascades was the predominant pathway; gigantol markedly inhibited the expression of complement component C9, which was a key component for the formation of terminal complement complex (TCC) C5b-9. These results were validated by immunohistochemistry (IHC) or real time-PCR. Confocal microscopy analysis showed that gigantol significantly inhibited the vascular deposition of TCC in the liver. In conclusion, we demonstrate for the first time that oral administration of gigantol potently relieves liver oxidative stress and inflammation, possibly via a novel mechanism of inhibiting the C5b-9 formation in the liver.

关键词gigantol Chinese traditional medicine liver injury oxidative stress inflammation label-free proteomic complement and coagulation cascades terminal complement complex
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Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000532622200002
出版者NATURE PUBLISHING GROUP
WOS关键词MEMBRANE ATTACK COMPLEX ; FATTY LIVER ; REACTIVE OXYGEN ; NITRIC-OXIDE ; INJURY ; EXPRESSION ; GENE ; BILE ; C3 ; ACETYLCYSTEINE
原始文献类型Article
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/121080
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, Guo-yu
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, State Key Lab Drug Res & Nat Prod, Chem Dept, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.SIMM CUHK Joint Res Lab Promoting Globalizat Trad, Shanghai 201203, Peoples R China
5.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, Ya-ru,Yao, Sheng,Liu, Qian,et al. Dihydro-stilbene gigantol relieves CCl4-induced hepatic oxidative stress and inflammation in mice via inhibiting C5b-9 formation in the liver[J]. ACTA PHARMACOLOGICA SINICA,2020.
APA Xue, Ya-ru.,Yao, Sheng.,Liu, Qian.,Peng, Zhao-liang.,Deng, Qiang-qiang.,...&Pan, Guo-yu.(2020).Dihydro-stilbene gigantol relieves CCl4-induced hepatic oxidative stress and inflammation in mice via inhibiting C5b-9 formation in the liver.ACTA PHARMACOLOGICA SINICA.
MLA Xue, Ya-ru,et al."Dihydro-stilbene gigantol relieves CCl4-induced hepatic oxidative stress and inflammation in mice via inhibiting C5b-9 formation in the liver".ACTA PHARMACOLOGICA SINICA (2020).
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
个性服务
查看访问统计
谷歌学术
谷歌学术中相似的文章
[Xue, Ya-ru]的文章
[Yao, Sheng]的文章
[Liu, Qian]的文章
百度学术
百度学术中相似的文章
[Xue, Ya-ru]的文章
[Yao, Sheng]的文章
[Liu, Qian]的文章
必应学术
必应学术中相似的文章
[Xue, Ya-ru]的文章
[Yao, Sheng]的文章
[Liu, Qian]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。