Study on the Toxicological Mechanism of Psoraleae Fructus Induced Liver Injury Based on Network Pharmacology and Cell Experiment

OBJECTIVE To explore the mechanism of Psoraleae Fructus (PF) induced liver injury by using network pharmacology.METHODS The potential toxic components of PF were screened by ETCM,CTD databases and literatures.The Swiss Target Prediction platform was used to predict the target related to components of PF.The target proteins related to liver injury were collected from GeneCards database.And the common target genes both related to the components of PF and liver injury were obtained.The protein-protein interaction network of PF was constructed,and the biological function enrichment analysis and molecular docking verification were carried out.The key targets of PF induced liver injury were verified by in vitro cell experiments.RESULTS A total of 25 potential toxic components of PF were screened,and 136 targets were combined with liver injury.Among them,PIK3CA,HSP90AA1,SRC,AKT1 and others,might be the key targets of liver injury induced by PF.The main signaling pathways related to liver injury induced by PF include PI3K-Akt signaling pathway,VEGF signaling pathway and HIF-1 signaling pathway,which might be caused by the regulation of cell apoptosis,adhesion plaque and bile secretion.Molecular docking results showed that the potential toxic components of PF had strong binding ability with key target proteins.In vitro cell experiments showed that the main components of PF could inhibit the mRNA expression of MAPK1,PIK3CA,AKT1 and JAK2,and cause liver injury.CONCLUSION The liver injury induced by PF has the characteristics of multi-component,multi-target and multi-pathways,which provides reference and basis for further elucidating the material basis and mechanism of liver injury induced by PF.