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Metabolomics reveals the role of PPAR alpha in Tripterygium Wilfordii-induced liver injury
Dai, Manyun1,2,3; Peng, Wan1,2,3,4; Zhang, Ting1,2,3; Zhao, Qi3; Ma, Xiaofang3; Cheng, Yan3; Wang, Chunyan3; Li, Fei1,3,5
Corresponding AuthorLi, Fei(feili@wchscu.cn)
2022-05-10
Source PublicationJOURNAL OF ETHNOPHARMACOLOGY
ISSN0378-8741
Volume289Pages:16
AbstractEthnopharmacological relevance: Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) have been used to treat autoimmune diseases clinically, however, the side effects of TWT are higher than TGT, especially for hepatotoxicity. The aim of the study: This study aims to determine the mechanism of TWT-induced liver injury. Materials and methods: We performed metabolomic analysis of samples from mice with liver injury induced by TGT and TWT. Ppara-null mice were used to determine the role of PPAR alpha in TWT-induced liver injury. Results: The results indicated that TWT induced the accumulation of medium- and long-chain carnitines metabolism, which was associated with the disruption of PPAR alpha-IL6-STAT3 axis. PPAR alpha agonists fenofibrate could reverse the liver injury from TWT and TP/Cel, and its protective role could be attenuated in Ppara-null mice. The toxicity difference of TWT and TGT was due to the different ratio of triptolide (TP) and celastrol (Cel) in the tablet in which TP/Cel was lower in TWT than TGT. The hepatotoxicity induced by TP and Cel also inhibited PPAR alpha and upregulated IL6-STAT3 axis, which could be alleviated following by PPAR alpha activation. Conclusions: These results indicated that PPAR alpha plays an important role in the hepatotoxicity of Tripterygium wilfordii, and PPAR alpha activation may offer a promising approach to prevent hepatotoxicity induced by the preparations of Tripterygium wilfordii.
KeywordTripterygium wilfordii Liver injury PPAR alpha IL6-STAT3 Metabolomics
DOI10.1016/j.jep.2022.115090
Indexed BySCI ; SCI
Language英语
WOS IDWOS:000811389800006
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/73846
Collection中国西南野生生物种质资源库
Corresponding AuthorLi, Fei
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Lab Metabol & Drug Induced Liver Injury, Chengdu 610041, Peoples R China
4.Sichuan Univ, Inst Rare Dis, West China Hosp, Chengdu 610041, Peoples R China
5.Sichuan Univ, Sichuan Univ Univ Oxford Huaxi Joint Ctr Gastroin, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network,Dept Ga, Chengdu 610041, Peoples R China
Recommended Citation
GB/T 7714
Dai, Manyun,Peng, Wan,Zhang, Ting,et al. Metabolomics reveals the role of PPAR alpha in Tripterygium Wilfordii-induced liver injury[J]. JOURNAL OF ETHNOPHARMACOLOGY,2022,289:16.
APA Dai, Manyun.,Peng, Wan.,Zhang, Ting.,Zhao, Qi.,Ma, Xiaofang.,...&Li, Fei.(2022).Metabolomics reveals the role of PPAR alpha in Tripterygium Wilfordii-induced liver injury.JOURNAL OF ETHNOPHARMACOLOGY,289,16.
MLA Dai, Manyun,et al."Metabolomics reveals the role of PPAR alpha in Tripterygium Wilfordii-induced liver injury".JOURNAL OF ETHNOPHARMACOLOGY 289(2022):16.
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