Exploring Ziziphus jujuba phytochemicals against oral cancer: Network-based profiling and molecular dynamics analyses

Oral cancer remains a major global health challenge due to its complex molecular heterogeneity, limited therapeutic efficacy, and high recurrence rate. This study aimed to identify potential multi-target natural therapeutics derived from Ziziphus jujuba using an integrative computational approach. Network pharmacology was employed to map phytochemical-target interactions relevant to oral oncogenic pathways, focusing on EGFR, BCL2, SRC, STAT3, and CTNNB1. Molecular docking was performed to evaluate binding affinities, followed by 200 ns molecular dynamics simulations and MM-GBSA analyses to assess complex stability and energetics. Among the screened compounds, oleanonic acid demonstrated the most favorable interaction profile, with docking scores of approximately -9.0 kcal/mol for BCL2 and -9.3 kcal/mol for EGFR, outperforming reference inhibitors. MD trajectories indicated stable RMSD plateaus, low active-site RMSF, and consistent Rg and SASA profiles, reflecting robust ligand-receptor stability. MM-GBSA results revealed dominant van der Waals and hydrophobic contributions to complex stabilization. Collectively, these findings highlight oleanonic acid as a promising multi-target phytochemical from Z. jujuba with potential therapeutic relevance in oral cancer. Further in vitro and in vivo studies are warranted to validate these computational predictions and advance its development as a candidate for oral cancer management.