Abstract
Oxidative stress plays a crucial role in the development of chronic and degenerative diseases due to an imbalance between reactive oxygen species (ROS) production and endogenous antioxidant defenses. Arcangelisia flava (Menispermaceae), a traditional medicinal plant widely used in Southeast Asia, is rich in furanoditerpenes with reported antioxidant and anti-inflammatory activities. This study aimed to elucidate the multitarget molecular mechanisms of A. flava furanoditerpenes using an integrated network pharmacology and molecular docking approach. Target prediction was performed using the SuperPRED database, while oxidative stress and inflammation-related genes were retrieved from GeneCards. Protein interaction analysis identified ten hub genes, including AKT1, TNF, EGFR, MTOR, and MAPK3, which are primarily involved in redox regulation and inflammatory signaling. Gene Ontology and KEGG pathway enrichment analyses highlighted the PI3K-Akt, MAPK, and NF-κB pathways as key regulatory mechanisms. Molecular docking validation demonstrated that jatrotthizine exhibited strong binding affinity to PI3K (PDB ID: 4HVB; –9.08 kcal/mol), comparable to the native inhibitor, with interactions involving critical catalytic residues. These findings confirm network pharmacology predictions and suggest that A. flava furanoditerpenes exert antioxidant and anti-inflammatory effects by coordinating modulation of the PI3K-Akt-NF-κB signaling axis. This study provides molecular evidence supporting the traditional use of A. flava and identifies jatrotthizine as a promising lead compound for further pharmacological development.