A Study of NMR-Based Hepatic and Serum Metabolomics in a Liver Injury Sprague-Dawley Rat Model Induced by Psoralen

摘要

Psoralen is the main active component of Psoralea corylifolia and is used as a marker to assess its quality. The effects of psoralen on animals have been well characterized. However, the molecular pathway of its toxicity is not fully understood. In this study, the toxic effects of psoralen administration (60 mg/kg) for 7 days in Sprague-Dawley rats were observed. Serum biochemistry and liver histopathology were further investigated. Proton nuclear magnetic resonance was applied to characterize the metabolic profile of liver toxicity induced by psoralen and to find changed metabolites in rat serum and liver. It was revealed that visceral coefficients and serum biochemistry indexes were significantly changed in rats with psoralen-induced liver injury. Furthermore, the histopathological examination exhibited that the liver might be the target organ for psoralen. Metabolic analysis of both serum and liver samples further proved the liver was the target of toxicity of psoralen. Multivariate analysis identified 7 metabolites in serum samples and 15 in liver samples as potential biomarkers in liver injury induced by psoralen. In addition, our results suggest that psoralen can cause a disturbance in amino acid metabolism, especially valine, leucine, and isoleucine biosynthesis in both serum and liver samples. In conclusion, we combined the results of toxicity and metabolomics induced by psoralen and provide useful information about the safety and potential risks of psoralen and Psoralea corylifolia.