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Metabolomic Responses of Human Hepatocytes to Emodin,Aristolochic Acid,and Triptolide: Chemicals Purified from Traditional Chinese Medicines
Authors:Xiaoyan Liu  Yanqiu Liu  Mengchun Cheng  Hongbin Xiao
Institution:1. Key Laboratory of Separation Science for Analytical Chemistry, Da lian Institute of Chemical Physics, Chinese Academy of Science, Dalian, People's Republic of China;2. Graduate Division, University of Chinese Academy of Sciences, Beijing, People's Republic of China;3. College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, People's Republic of China;4. Systems Analysis and Innovative Drug Research Center, Beijing University of Chinese Medicine, Beijing, People's Republic of China
Abstract:The present study was undertaken to investigate the metabolic responses of human liver cells HL‐7702 on chemicals purified from traditional Chinese medicine: emodin, triptolide, and aristolochic acid. Cytotoxicity tests demonstrated a dose‐dependent toxic effect of emodin, triptolide, and aristolochic acid on HL7702 cells for 48 h. Emodin (14 μM), aristolochic acid (12 μg/mL), or triptolide (18 nM) was individually administrated to HL7702 and cell samples were collected after 48 h for metabolites extraction and analysis. Pattern recognition analysis reflected the significant difference in metabolic profiles between chemical‐treated groups and the control group. Finally, eight metabolites including N1‐acetylspermidine, Glu Gly, N‐undecanoylglycine, C16 sphinganine, sphinganine, glutathione, l ‐palmitoylcarnitine, and elaidic carnitine were detected as potential common biomarkers. Three pathways including sphinganine metabolism, fatty acid oxidation, and oxidative stress were identified. Our findings indicated that metabolomics would be an efficient approach to understand the molecular mechanism of hepatotoxicity induced by chemicals.
Keywords:Metabolomics  Hepatotoxicity  HL‐7702  Hepatotoxicants
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