2. Academic Validation
  3. Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling

Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling

  • Mol Cell Proteomics. 2019 Mar;18(3):520-533. doi: 10.1074/mcp.RA118.000817.
Qi Zhao 1 2,  Fang Liu 1,  Yan Cheng 1,  Xue-Rong Xiao 1,  Dan-Dan Hu 1,  Ying-Mei Tang 3,  Wei-Min Bao 4,  Jin-Hui Yang 5,  Tao Jiang 5,  Jia-Peng Hu 6,  Frank J Gonzalez 7,  Fei Li 8 9
Affiliations

Affiliations

  • 1 From the ‡State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
  • 2 §University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 ¶Department of Gastroenterology, The 2nd Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming 650033, China; [email protected].
  • 4 ‖Department of General Surgery, Yunnan Provincial 1st People's Hospital, Kunming 650032, China.
  • 5 ¶Department of Gastroenterology, The 2nd Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming 650033, China.
  • 6 **Clinical Laboratory, The 2nd Affiliated Hospital of Kunming Medical University, Kunming 650033, China.
  • 7 ‡‡Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
  • 8 From the ‡State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; [email protected].
  • 9 §§State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, Jiangsu, China.
PMID: 30617157 DOI: 10.1074/mcp.RA118.000817
Abstract

Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by α-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate Sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in FXR-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.

Keywords

Hepatotoxicity; Mass Spectrometry; Mechanism of action; Metabolites; Metabolomics.

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