OBJECTIVE To systematically explore the pharmacodynamic material basis and molecular mechanism of Sophora moorcroftiana, a characteristic ethnic medicine from Xizang, as well as its core active ingredient medicarpin against hepatocellular carcinoma(HCC).

METHODS The chemical constituents of S. moorcroftiana were collected through literature mining and previous mass spectrometry identification. Active molecules and HCC-related disease targets were screened using network pharmacology. A protein-protein interaction(PPI) network was constructed, and topological analysis was performed to identify core targets. Gene ontology(GO) functional annotation and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted using the DAVID database. Molecular docking verification of the core components and key targets was performed using AutoDock Vina. Human hepatoma HepG2 cells were cultured in vitro. The effects of medicarpin on cell proliferation and apoptosis were evaluated by MTT assay, colony formation assay, and Hoechst 33258 staining. Western blotting was employed to detect the expression and phosphorylation levels of proteins related to the SRC/STAT3 and AKT pathways.

RESULTS Network pharmacology prediction indicated that S. moorcroftiana might exert its anti-HCC effects mainly through the PI3K/AKT and SRC/STAT3 signaling pathways, with SRC, HSP90AA1, STAT3, MAPK1, and AKT1 identified as the core targets. Molecular docking results suggested that medicarpin had favorable potential binding capacity to these core targets. In vitro cell experiments showed that medicarpin significantly inhibited HepG2 cell proliferation in a concentration- and time-dependent manner. Western blotting analysis showed that medicarpin markedly reduced the Bcl-2/Bax ratio and induced HCC cell apoptosis by significantly suppressing SRC/STAT3 activation and AKT phosphorylation.

CONCLUSION As a vital bioactive ingredient of S. moorcroftiana, medicarpin exhibits prominent anti-HCC activity. This study conducts multi-dimensional verification based on the “drug active ingredient-target-pathway-disease” network, which provides theoretical and experimental evidences for the development of novel anti-hepatocellular carcinoma drugs derived from S. moorcroftiana and its active compounds.