Hedyotis diffusae herba -Scutellaria Barbata herba drug pair suppresses prostate cancer by inducing apoptosis.

Prostate cancer (PCa), a globally prevalent male malignancy, necessitates breakthroughs in treating its hormone-refractory stage. The Traditional Chinese Medicine drug pair Hedyotis Diffusae Herba - Scutellaria Barbatae Herba (HDH-SBH) shows significant antitumor value, but its multi-component synergistic mechanisms remain unclear. This study elucidated HDH-SBH's molecular mechanisms in suppressing PCa via apoptosis pathways. Network pharmacology predicted active components (quercetin, ursolic acid, apigenin) and core targets (AKT1, BCL2, NFKB) enriched in apoptosis (P < 0.05). Molecular docking revealed strong binding (e.g., ursolic acid-AKT1: -7.76 kcal/mol), confirmed by stable 100 ns molecular dynamics simulations (RMSD < 5.0 Å). In vitro, HDH-SBH significantly inhibited PC-3 cell proliferation (48 h IC = 1.094 mg/mL), reduced migration (36 h rate decreased by 64.2%), and induced apoptosis (rate 13.57% vs. control 4.79%). It downregulated BCL2 and p-65 protein expression (P < 0.05) while suppressing AKT1 phosphorylation. Thus, HDH-SBH targets the AKT1/BCL2/NFKB axis to regulate apoptosis and suppress PCa progression, providing a theoretical and experimental foundation for modernizing TCM in antitumor research.