Integrative proteomics-metabolomics strategy reveals the mechanism of hepatotoxicity induced by Fructus Psoraleae.

Fructus Psoraleae (FP), one of the significant traditional Chinese medicines, has been reported to cause hepatotoxicity. However, the mechanism remains undetermined and the reported research is limited. In this study, a tandem mass tag (TMT)-based quantitative proteomics and metabolomics were used to reveal a more comprehensive effect caused by FP. The results showed that aqueous extract of FP can induce liver injury in rats. In total, 575 significantly changed proteins were identified by quantitative proteomics analysis, among which 352 proteins were significantly up-regulated and 223 proteins were significantly down-regulated in liver tissues. And we detected 14 biomarkers such as succinic acid, hypoxanthine, l-carnitine, phenylalanine, glutathione, and glycoursodeoxycholic acid. Correlation analysis of altered metabolites and proteins exhibited the aberrant regulation of metabolic pathways including bile secretion, glutathione metabolism, purine metabolism, glycerophospholipid metabolism, TCA cycle and pyruvate metabolism, which indicated the disorder of bile acid metabolism, oxidative stress, energy metabolism and immune system. Notably, the changed proteins including Cyp7a1, FXR, SHP, BSEP, Sult2a1, Nceh1 in bile acid metabolism may play an essential role in the hepatotoxicity induced by aqueous extract of FP. In conclusion, integrative proteomics and metabolomics provide the potential mechanism of hepatotoxicity induced by FP.