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Liver-specific metabolomics characterizes the hepatotoxicity of Dioscorea bulbifera rhizome in rats by integration of GC-MS and 1H-NMR

Zhao, Dong-Sheng, Wu, Zi-Tian, Li, Zhuo-Qing, Wang, Ling-Li, Jiang, Li-Long, Shi, Wei, Li, Ping, Li, Hui-Jun
Journal of ethnopharmacology 2018
Dioscorea bulbifera, amino acids, bile acids, biochemical pathways, biomarkers, gas chromatography-mass spectrometry, hepatotoxicity, herbal medicines, intestinal microorganisms, lipids, liver, metabolites, metabolomics, multivariate analysis, neoplasms, nuclear magnetic resonance spectroscopy, pharyngitis, rats, rhizomes, traditional medicine
Dioscorea bulbifera rhizome (DBR), one type of herbal medicine, is extensively used in both Indian and Chinese system of traditional medicine. It has been effective in treating various diseases, such as sore throat, struma, and tumors. However, more and more clinical investigations have suggested that DBR can cause liver injury.In the present study, we aimed to characterize the corresponding molecular changes of liver dysfunction and reveal overall metabolic and physiological mechanisms of the subchronic toxic effect of DBR.A liver-specific metabolomics approach integrating GC-MS and ¹H-NMR was developed to assess the hepatotoxicity in rats after DBR exposure for 12 weeks. Multivariate statistical analysis and pattern recognition were employed to examine different metabolic profiles of liver in DBR-challenged rats.A total of 61 metabolites were screened as significantly altered metabolites, which were distributed in 43 metabolic pathways. The correlation network analysis indicated that the hub metabolites of hepatotoxicity could be mainly linked to amino acid, lipid, purine, pyrimidine, bile acid, gut microflora, and energy metabolisms. Notably, purine, pyrimidine, and gut microflora metabolisms might be novel pathways participating in metabolic abnormalities in rats with DBR-triggered hepatic damage.Our results primarily showed that the liver-specific metabolic information provided by the different analytical platforms was essential for identifying more biomarkers and metabolic pathways, and our findings provided novel insights into understand the mechanistic complexity of herb-induced liver injury.