Abstract
Oral cancer (OC) remains a significant global health concern due to its high incidence and mortality. Quercus infectoria (QI), a traditional medicinal plant, harbors bioactive compounds with potential anticancer properties. This study systematically integrates multiple computational and experimental approaches to identify and validate the anticancer potential of QI phytoconstituents. Network pharmacology was used to predict key molecular targets and signaling pathways, notably apoptosis and the PI3K-Akt pathway-providing mechanistic validation through pathway-level insights into anticancer activity. Molecular docking revealed strong binding affinities of Nyctanthic acid (-125.426 and -113.841 kcal/mol) and β-Glucogallin (-96.7558 and -112.534 kcal/mol) with AKT1 and GAPDH, respectively. Molecular dynamics (MD) simulations further confirmed the structural validation by demonstrating the stability and conformational integrity of these protein-ligand complexes. Cellular validation was achieved through cytotoxic assay on KB oral cancer cells, which showed dose-dependent cytotoxicity, with IC(50) values of 224.41 ± 2.01 μg/mL for the QI extract and 213.77 ± 1.98 μg/mL for Cisplatin. Density Functional Theory (DFT) analysis further supported the electronic stability and reactivity of Nyctanthic acid. From the study, Nyctanthic acid showed the superior binding affinity, target relevance (AKT1), and computational stability that make it a promising multi-target anticancer candidate. These findings lay the groundwork for future in vivo studies, formulation development, and translational drug development.