Metabolomic Responses of Human Hepatocytes to Emodin, Aristolochic Acid, and Triptolide: Chemicals Purified from Traditional Chinese Medicines

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 mu M), aristolochic acid (12 mu g/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. (C) 2015 Wiley Periodicals, Inc.