Molecular mechanisms of Psoraleae Fructus-induced liver injury: insights from computational toxicology and transcriptomics analysis

As a commonly used Traditional Chinese Medicine in Asian countries, Psoraleae Fructus (PF) has demonstrated satisfactory efficacy in treating various refractory diseases. However, in recent years, frequent reports of PF-related liver injury significantly limited its clinical application. Therefore, research efforts to address the hepatotoxicity of PF should be encouraged. In this study, we systematically investigated the material basis and mechanisms of PF-induced liver injury by integrating computational toxicology and transcriptomics. As a result, a total of 14 blood constituents, primarily coumarins and flavonoids, were identified as the major hepatotoxic components of PF. TP53, BCL2, CASP3, MYC, EGFR, MMP9, ALB, and GAPDH were determined to be the hub genes. Mechanistically, KEGG enrichment analysis, module function analysis, and hub gene analysis consistently indicated that apoptosis plays a critical role in PF-induced liver injury.