Investigation of the mechanism of hepatotxicity induced by Fructus Psoraleae combined with UPLC-QTOF-MS and network toxicology technology / 国际药学研究杂志

ABSTRACT

Objective: To analyze and identify the chemical constituents from Fructus Psraleae(FP)in the rat liver after intragastric FP administration, and explore the potential mechanism of FP- induced hepatotoxicity via the network toxicology study. Methods: UPLC-QTOF-MS and UNIFI data screening platform were used to quickly identify the chemical constituents from FP in the rat liver afte intragastric FP administration, and multiple databases were used to search for information about chemical component targets, hepatotoxic targets, component hepatotoxic common targets and indirect targets. The construction of protein protein interaction (PPI)network and the enrichment analysis of gene ontology(GO)biological function and Kyoto Encycolpenia of Genes and Genomes (KEGG)pathway were carried out on the searched targets by using the String database and Cytoscape 3.6.1 software to explore the key targets and potential mechanism of hepatotoxicity induced by constituents from FP. Results: Eleven prototypic components of FP were identified in the rat liver. The network toxicology studies showed that there were a total of 52 potential targets and 23 pathways for the FP hepatotoxicity, among which ALB, HOMX1, GSR, GSTM3 and CYP2C9 targets, as well as the thyroid synthesis pathway and the glutathione metabolism pathway had a strong correlation with the FP hepatotoxicity. Conclusion: By UPLC-QTOF-MS combined with the UNIFI platform, the 11 chemical constituents from FP could be quickly identified in the liver of rats that were intragastrically administered FP, and the network toxicology study has predicted potential molecular mechanism of the hepatotoxicity induced by FP. The present results provide a reference for further study the hepatotoxicity of FP.