Network Pharmacology and Molecular Insights into Artemetin and Vitrofolal E of Vitex negundo against Diabetic Cardiomyopathy

Abstract Artemetin and Vitrofolal E are phytoconstituents of the Vitex negundo (VN) plant, which is extensively used in traditional medicine and is known for its broad spectrum of pharmacological activities. Several studies have determined the pharmacological effects of phytoconstituents present in the VN extract. However, the therapeutic potential of these phytoconstituents in treating diabetic cardiomyopathy (DCM) remains unexplored and demands further investigation. This study utilizes network pharmacology to identify Vitex negundo phytochemicals with potential therapeutic effects against DCM. Disease‐associated genes were sourced from GeneCards, DisGeNet, and OMIM, while compound‐target predictions were performed using SwissTargetPrediction. Enrichment analysis was performed using GO and KEGG, and protein–protein interactions were explored via String‐db and Cytoscape. Artemetin and Vitrofolal E exhibited strong target interactions with high probability scores. ADMET and drug‐likeness evaluations further supported their potential. Enrichment analysis revealed significant involvement in DCM‐related pathways (p < 0.01). To validate docking interactions, molecular dynamics simulations and MM‐GBSA were performed using Schrödinger, revealing robust binding affinities. This study investigates the interactions of Artemetin and Vitrofolal E with SLC5A1 and AR genes, identified based on their highest degree scores. The findings suggest promising therapeutic action; however, a thorough investigation via preclinical and clinical studies is important to substantiate these findings.