Multi-target modulation of prostate cancer signaling by Boerhavia diffusa leaf constituents: Insights from network pharmacology-guided in silico and in vitro approaches

Abstract

Prostate cancer (PC) remains a leading cause of male cancer mortality, and current treatments are frequently constrained by resistance, toxicity, and cost. Boerhavia diffusa (Punarnava) is widely used in traditional medicine, but its precise molecular mechanisms in PC are not well defined. This study integrated LC/MS-based phytochemical profiling, network pharmacology, molecular docking, and in vitro cytotoxicity to clarify the multi-target anticancer potential of B. diffusa leaf. LC/MS of the ethanolic extract tentatively identified eight major constituents; perakine and canavalioside were prioritized for systems analysis based on drug-likeness. Predicted targets (SwissTargetPrediction) were merged with PC genes (GeneCards) to generate a STRING-Cytoscape interaction network, revealing 10 hub nodes [epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3, caspase 3, AKT serine/threonine kinase 1 (AKT1), heat shock protein 90 alpha family class A member 1, catenin beta 1, BCL?2?like protein 1, SRC, insulin?like growth factor 1 receptor, and matrix metalloproteinase 2] enriched in PI3K-Akt, EGFR, and matrix-remodeling pathways. Docking showed that canavalioside binds AKT1 more strongly than perakine, while perakine exhibits a slightly more favorable docking score for PI3Kα; together, the two ligands form dense hydrogen?bond networks within functionally relevant regions of the PI3K?Akt axis. Consistently, the ethanolic B. diffusa leaf extract reduced PC-3 cell viability in a concentration-dependent manner with an IC50 of 57.213 μg/ml, providing preliminary functional support for the predicted multi-target antiproliferative activity.