期刊
XENOBIOTICA
卷 51, 期 6, 页码 716-727出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/00498254.2021.1900626
关键词
Tripterygium wilfordii; liver injury; farnesoid X receptor; bile acid metabolism; metabolomics
资金
- National Key Research and Development Program of China [2017YFC1700906, 2017YFC1702900]
- Double Thousand Program of Jiangxi Province [jxsq2018102022]
The study found that liver injury induced by Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) was associated with bile acid metabolism disorder, with inhibition of the farnesoid X receptor (FXR) signalling pathway being a key factor. Treatment with the FXR agonist obeticholic acid (OCA) could alleviate liver injury by activating FXR to inhibit related pathways and improve bile acid metabolism disorder caused by Tripterygium wilfordii preparations.
Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) are the preparations of Tripterygium wilfordii used to treat rheumatoid arthritis (RA) in the clinic, but the hepatotoxicity was reported frequently. This study aimed to determine the potential toxicity mechanism of liver injury induced by the preparations of Tripterygium wilfordii in mice. Here, we performed metabolomic analysis, pathological analysis and biochemical analysis of samples from mice with liver injury induced by TGT and TWT, which revealed that liver injury was associated with bile acid metabolism disorder. Quantitative real-time PCR (QPCR) and western blot indicated that the above changes were accompanied by inhibition of farnesoid X receptor (FXR) signalling. Liver injury from TWT could be alleviated by treatment of the FXR agonist obeticholic acid (OCA) via activation of the FXR to inhibit the c-Jun N-terminal kinase (JNK) pathway and improve bile acid metabolism disorder by activating bile salt export pump (BSEP) and organic solute-transporter-beta (OSTB). The data demonstrate that FXR signalling pathway plays a key role in T. wilfordii-induced liver injury, which could be alleviated by activated FXR. These results indicate that FXR activation by OCA may offer a promising therapeutic opportunity against hepatotoxicity from the preparations of T. wilfordii.
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