Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling
Year: 2019
Type: article
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.
Source: Molecular & Cellular Proteomics
Authors: Qi Zhao, Fang Liu, Yan Cheng, Xue-Rong Xiao, Dan-Dan Hu, Ying-Mei Tang, Wei-Min Bao, Jin-Hui Yang, Tao Jiang, Jia-Peng Hu, Frank J. Gonzalez, Fei Li
Institutions: Kunming Institute of Botany, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Second Affiliated Hospital of Kunming Medical College, First People's Hospital of Yunnan Province, National Institutes of Health, National Cancer Institute, Center for Cancer Research, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G254098712, G7321694426, G927322038
OpenAlex ID: W2909718701