Total Saponins from Aralia armata (Wall.) Seem to Act via the Wnt/β-Catenin Signaling Pathway: Network Pharmacology and ExperimentalValidation

Introduction: This study investigates how Aralia armata total saponins (AAS) inhibit SKOV3 ovarian cancer cells, focusing on Wnt/β-catenin pathway disruption. Both computational and experimental methods were applied to examine this mechanism. Methods: This study employed network pharmacology to predict AAS targets, identifying Wnt/β-catenin pathway components via PPI network, GO, and KEGG analyses. Molecular docking demonstrated strong binding of oleanolic acid—AAS’s main aglycone—to Axin, β-catenin, TCF, GSK3β, and Wnt2α. Experimental validation included CCK-8 cytotoxicity, Annexin V/PI apoptosis, cell cycle, Transwell migration/invasion assays, and RT-qPCR/WB quantification of key targets, confirming the inhibitory effects. Results: Molecular docking confirmed strong binding of oleanolic acid to Wnt targets. AAS dose-dependently inhibited SKOV3 proliferation, induced G0/G1 arrest and markedly promoted apoptosis (p< 0.01), and significantly suppressed migration/invasion (p< 0.01). Mechanistically, AAS blocked β-catenin nuclear translocation, evidenced by reduced nuclear Wnt signaling components (β-catenin, TCF-1, Axin2, Cyclin D1) and accumulated cytosolic β-catenin Discussion: AAS inhibits SKOV3 cell proliferation, migration, and invasion while inducing apoptosis through suppression of the Wnt/β-catenin signaling pathway. Network pharmacology and experimental validation demonstrate that AAS blocks β-catenin nuclear translocation and downregulates downstream effectors. These findings identify AAS as a promising TCM-derived candidate for ovarian cancer therapy Conclusion: AAS exerts anti-ovarian cancer effects by impeding β-catenin nuclear translocation through inhibition of the Wnt pathway, resulting in coordinated downregulation of oncogenic effectors and dual suppression of proliferation and metastasis. Furthermore, this mechanism effectively induces apoptosis and cell cycle arrest in SKOV3 cells, highlighting its multifaceted antitumor potential.