Network pharmacology prediction and experiment validation to discover the mechanism of Sophora japonica Linn. against liver cancer.

Sophora japonica Linn., a medicinal and food-homologous plant, is commonly used to resist bacterial, inflammatory, tumor, and other effects. This study aimed to elucidate the multi-target mechanism of action of Sophora japonica Linn. on liver cancer through network pharmacological analysis and verify its effect through biological experiments. The network pharmacology and molecular docking results showed that there were 152 interactivity targets between Sophora japonica Linn. and liver cancer, which were mainly enriched in various biological processes through the AKT and MAPK signaling pathways. In vitro biological experiments showed that isorhamnetin and quercetin, the main active components of Sophora japonica Linn., had significant inhibitory effect on liver cancer cells HepG2. In addition, the expression of AKT and MEK proteins was downregulated, which proved that both isorhamnetin and quercetin promoted apoptosis by activating the AKT and MAPK signaling pathways. In summary, our findings clarify the inhibitory effect of the active ingredients of Sophora japonica Linn. against HepG2 cells and provide inspiration for its clinical application in the treatment of liver cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00766-y.