FXR activation prevents liver injury induced by Tripterygium wilfordii preparations

Abstract

1. 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.

2. 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.

3. 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-β (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.

4. These results indicate that FXR activation by OCA may offer a promising therapeutic opportunity against hepatotoxicity from the preparations of T. wilfordii.

Keywords:

• Tripterygium wilfordii
• liver injury
• farnesoid X receptor
• bile acid metabolism
• metabolomics

Author contributions

Wan Peng, Manyun Dai and Lijuan Bao performed the experiments, data collection, statistical analysis and data interpretation and wrote the manuscript; Fei Li and Wei-Feng Zhu reviewed and edited the final draft, and provided the fundings. All authors have read and approved the final draft.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [2017YFC1700906 and 2017YFC1702900] and Double Thousand Program of Jiangxi Province [jxsq2018102022].