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Celastrol ameliorates acute liver injury through modulation of PPARα.

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机构： [a]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China [b]University of Chinese Academy of Sciences, Beijing 100049, China [c]Academician Workstation, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, China [d]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States [e]Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu 610065, China

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关键词： Celastrol Acute liver injury PPARα Metabolomics LC-MS

摘要：

Celastrol, derived from the roots of the Tripterygium Wilfordi, has attracted interest for its potential anti-inflammatory and lipid-lowering activities. In the present study, the protective effect of celastrol on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Celastrol improved the increased transaminase activity, inflammation, and oxidative stress induced by CCl4, resulting in improved metabolic disorders found in mice with liver injury. Dual-luciferase reporter assays and primary hepatocyte studies demonstrated that the peroxisome proliferator-activated receptor α (PPARα) signaling mediated the protective effect of celastrol, which was not observed in Ppara-null mice, and co-treatment of wild-type mice with the PPARα antagonist GW6471. Mechanistically, PPARα deficiency potentiated CCl4-induced liver injury through a deoxycholic acid (DCA)-EGR1-inflammatory factor axis. These data demonstrate a novel role for celastrol in protection against acute liver injury through modulating PPARα signaling. Copyright © 2020. Published by Elsevier Inc.

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出版当年[2020]版：

大类 | 2 区

医学

小类 | 2 区药学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区药学

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第一作者机构： [a]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

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通讯作者：

通讯机构： [a]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China [e]Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu 610065, China [*1]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

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Celastrol ameliorates acute liver injury through modulation of PPARα.

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