UPLC/Q-TOFMS-Based Metabolomics Studies on the Protective Effect of Panax notoginseng Saponins on Alcoholic Liver Injury

摘要

Consistent, excessive alcohol consumption leads to liver injury. The aim of the present study is to evaluate the possible efficacy of Panax notoginseng saponins (PNS) against chronic alcohol-induced liver injury using LC-MS-based urinary metabolomics. Mice were fed a Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin as a control diet with or without PNS (200 mg/kg/BW) for 4 weeks. Treatment with PNS significantly reduced the increases in plasma ALT and AST levels, hepatic levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which induced by chronic alcohol exposure. Conversely, PNS was also found to restore the glutathione (GSH) depletion and increase the superoxide dismutase (SOD) activities. The end-point urine sample of each mouse was collected overnight (24 h) in metabolic cages and their metabolic profiling changes were analyzed using UPLC/Q-TOFMS followed by multivariate statistical analysis. After 4 week of Lieber-DeCarli alcohol diet feeding, the metabolic profile experienced great perturbation in PCA score plot, and the treatment of PNS could assist to regulate the disturbed metabolic profile induced by alcohol exposure. Additionally, sixteen potential biomarkers responsible for derivations of the metabolic profile induced by alcohol exposure were identified, and the alcohol-induced changes in these biomarkers, except hexanoylglycine, could be partially or nearly reversed by PNS treatment. Taken together, PNS protects against chronic alcohol-induced liver injury. Our findings demonstrated that the LC-MS-based metabolomics approach is a useful tool to investigate the efficacy of Chinese medicines.