Mechanism of action of triterpenoid saponins from Palaquium formosanum for prostate cancer treatment: Insights from network pharmacology, molecular docking, and dynamics simulations

Abstract

Prostate cancer continues to pose a formidable global health challenge, driving the need for innovative, low-toxicity therapeutic strategies. Natural compounds from traditional herbal origins, notably triterpenoid saponins, demonstrate promise in cancer care by curbing proliferation, triggering apoptosis, and influencing critical signaling pathways. This investigation delved into the mechanism of triterpenoid saponins from Palaquium formosanum as potential anti-prostate cancer agents, targeting the myeloid cell leukemia-1 protein (MCL-1, protein ID: 6QGG), with insights derived from network pharmacology, molecular docking, and molecular dynamics simulations. Network pharmacology analysis identified key molecular targets and pathways, providing a comprehensive framework for understanding the saponins' biological impact. Molecular docking revealed that CPD1 and CPD5 exhibit enhanced binding affinities compared to 5FU, suggesting their ability to modulate apoptosis resistance. Molecular dynamics simulations further confirmed stable interactions, with parameters including RMSD, RMSF, Rg, Hbonds, and SASA reinforcing the robustness of the complexes. These findings position CPD1 and CPD5 as promising MCL-1 inhibitors for prostate cancer intervention. Additionally, they establish a foundation for designing novel derivatives with improved potency and safety profiles, awaiting validation through in vitro and in vivo studies.