Network pharmacology, pathway enrichment, and molecular docking analysis reveal the multi target therapeutic potential of phytochemicals from Eleusine coracana

Abstract Eleusine coracana (L.) Gaertn., commonly known as Ragi or finger millet, is a nutrient-rich cereal traditionally valued for its health-promoting properties. However, its precise molecular mechanisms and therapeutic targets remain inadequately understood. This study employed an integrated network pharmacology approach combined with ADMET screening, Gene Ontology (GO), KEGG pathway, and molecular docking analyses to elucidate the molecular targets and biological pathways modulated by E. coracana phytochemicals. A total of 38 phytochemicals were initially retrieved from the IMPPAT and KNApSAcK databases. After applying Lipinski’s rule of five and safety profiling, 23 phytochemicals were selected, leading to the identification of 579 potential protein targets. Network analysis identified the top 10 hub genes, IL6, EGFR, ESR1, PPARG, CYCS, JUN, NFKB1, EP300, CCND1, and SNCA, which are associated with inflammation, apoptosis, metabolic regulation, and immune signaling. GO enrichment indicated significant involvement in responses to organic cyclic compounds, lipids, chemical stress, and transcriptional regulation, with targets primarily localized to chromatin, nuclear, and mitochondrial compartments. KEGG analysis highlighted pathways related to cancer, non-alcoholic fatty liver disease, atherosclerosis, and viral infections. Molecular docking demonstrated strong binding affinities of several phytochemicals toward IL6 and EGFR. Riboflavin (− 5.8 kcal/mol) and tricin (− 5.5 kcal/mol) showed superior binding to IL6, while violanthin and orientin (− 9.4 kcal/mol) exhibited the highest affinity for EGFR, surpassing reference ligands. Stable hydrogen bonding and hydrophobic interactions supported their inhibitory potential. Overall, these findings provide mechanistic insights into the multi-target potential of E. coracana phytochemicals and highlight their predicted functional relevance as a component of a functional food. However, further in vitro and in vivo validation is required to confirm their biological activity and therapeutic relevance.