NMR-based metabolomic approach to understanding Zeng-Sheng-Ping-induced hepatotoxicity, and identifying possible toxic constituents by LC-MS profiles

Zeng-Sheng-Ping (ZSP) tablets, made from six Chinese herbs, are widely used in the chemoprevention and treatment of precancerous lesions in patients with gastrointestinal cancer. However, sporadic cases of liver injury have occurred. Herein, the serum metabolites in hamsters with ZSP-induced liver damage were analyzed by NMR-based metabolomics. Twelve metabolites associated with ZSP-induced hepatoxicity were identified. Amino acid metabolism and the urea cycle were significantly altered, and three associated amino acid metabolic enzymes (PAH, GS, and GLS) were further validated by ELISA. Therefore, 12 metabolites and 3 amino acid metabolic enzymes were proposed as potential biomarkers in ZSP-induced liver injury. The chemical constituents of ZSP tablets were profiled using liquid chromatography-mass spectrometry. The furanoids in two herbs, Dioscorea bulbifera L. and Dictamnus dasycarpus Turcz., were proposed to be the major hepatotoxic constituents in ZSP, leading to an improved preparation method with low hepatotoxicity for ZSP. •Hepatotoxicity of Zeng-Sheng-Ping tablets was analyzed by NMR-based metabolomics.•Twelve metabolites were identified as biomarkers with amino acid pathways altered.•Three associated enzymes were validated by ELISA.•Hepatotoxic constituents were deduced based on chemical profile of LC-MS analysis.•This work provides a basis for preparing low-hepatotoxic Zeng-Sheng-Ping.