Metabolomic-transcriptomic landscape of 8-epidiosbulbin E acetate -a major diterpenoid lactone from Dioscorea bulbifera tuber induces hepatotoxicity

• Published in: Food and chemical toxicology Vol. 135; p. 110887
• Main Authors: Shi, Wei, Jiang, Yan, Zhao, Dong-Sheng, Jiang, Li-Long, Liu, Feng-Jie, Wu, Zi-Tian, Li, Zhuo-Qing, Wang, Ling-Li, Zhou, Jing, Li, Ping, Li, Hui-Jun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2020
• Subjects: 8-Epidiosbulbin E acetate; Animals; Bile acid metabolism; Biomarkers - metabolism; Chemical and Drug Induced Liver Injury - metabolism; Dioscorea - chemistry; Diterpenes - pharmacology; Diterpenes - toxicity; Gene Expression Regulation; Hepatotoxicity; Liver - drug effects; Male; Metabolomics; Mice; Mice, Inbred ICR; Transcriptome; transcriptomics; 8-Epidiosbulbin E acetate; transcriptomics; Metabolomics; Hepatotoxicity; Bile acid metabolism
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.110887

Studies have shown that 8-epidiosbulbin E acetate (EEA), a major diterpenoid lactone in the tuber of Dioscorea bulbifera, can induce hepatotoxicity in vivo. However, the underlying mechanisms remain unknown. Using the integrated transcriptomic and metabolomics method, in this study we investigated the global effect of EEA exposure on the transcriptomic and metabolomic profiles in mice. The abundance of 7131 genes and 42 metabolites in the liver, as well as 43 metabolites in the serum were altered. It should be noted that EEA mainly damaged hepatic cells through the aberrant regulation of multiple systems primarily including bile acid metabolism, and taurine and hypotaurine metabolism. In addition, an imbalance of bile acid metabolism was found to play a key pat in response to EEA-triggered hepatotoxicity. In summary, these findings contributed to understanding the underlying mechanisms of EEA hepatotoxicity. •An integrated transcriptomic/metabolomics method for screening EEA hepatotoxicity.•Purine and pyrimidine metabolisms might be the novel metabolic pathways for EEA-induced hepatotoxicity.•Imbalance of bile acid metabolism might be responsible for EEA-induced hepatotoxicity.•TCA and CA along with CDCA could be considered as biomarkers.