Tetrapleura tetraptera fruit (Schumach. & Thonn.) Taub. as a prospective anti-prostate cancer agent revealed through network pharmacology, molecular docking and dynamics, and in vitro studies

Ethnopharmacology relevance: Cancer is a major global public health concern with significant ramifications on quality of life and treatment outcomes. Medicinal plants such as Tetrapleura tetraptera (TT) are key sources of bioactive compounds with therapeutic potential, yet their efficacy and underlying molecular mechanisms remain largely unexplored. Aim of the study: To investigate the anti-prostate cancer potential, antioxidant activity, and underlying mechanism of TT. Materials and methods: Crude extracts were obtained through the sequential extraction of powdered TT (whole fruit, pulp, and seed). TT extracts were assessed for their antioxidant activity, total phenolic content and antiprostate cancer activity using the DPPH radical scavenging assay, Folin-Ciocalteu method and tetrazolium-based colorimetric assay, respectively. Bioactive compounds from TT and prostate cancer-related targets were identified through literature mining and public databases. Network pharmacology, molecular docking and molecular dynamics were employed to elucidate TT's potential mechanisms of action. Results: Aqueous whole fruit extract exhibited potent antioxidant activity with EC₅₀ = 83.46 ± 1.07 μg/mL, while the ethyl acetate fruit extract showed the strongest anti-prostate cancer activity (PC3 IC₅₀ = 5.39 ± 1.24 μg/mL, SI = 7.72; LNCaP IC₅₀ = 8.38 ± 1.27 μg/mL, SI = 4.97). Network pharmacology revealed that TT compounds targeted key proteins within the prostate cancer pathway, implicating MAPK, PI3K/AKT and P53 signaling cascades. Molecular docking and dynamics simulations further supported these findings, demonstrating strong, stable and flexible binding interactions between luteolin with MMP9/AR and Scopoletin with ERBB2. Conclusions: Whole TT fruit demonstrates promising anti-prostate cancer activity through the multitargeted modulation of key proteins involved in pivotal signaling pathways. However, further in vitro, in vivo and clinical studies are required to validate these findings and fully explore TT's therapeutic potential.