MULTITARGET NEUROPROTECTIVE POTENTIAL OF PHYTOCOMPOUNDS FROM GLYCYRRHIZA GLABRA: A NETWORK PHARMACOLOGY AND MOLECULAR DYNAMICS STUDY

Abstract

Neurodegenerative disorders are characterized by progressive neuronal loss associated with oxidative stress, neuroinflammation, apoptosis, and amyloid-beta accumulation. The present study aimed to investigate the neuroprotective potential of phytoconstituents identified from the ethanolic root extract of Glycyrrhiza glabra using an integrated GC–MS, network pharmacology, molecular docking, and molecular dynamics simulation approach. GC–MS analysis identified 43 phytocompounds, among which five biologically relevant compounds were selected for in silico analysis. Network pharmacology and protein–protein interaction analysis identified key hub genes including AKT1, EGFR, and BACE-1 associated with apoptosis, neuroinflammation, oxidative stress, and amyloid-beta response pathways. Functional enrichment analysis further confirmed the involvement of Alzheimer disease, neurotrophin signaling, and apoptotic pathways in neurodegenerative progression. Molecular docking studies revealed that 4H-pyran-4-one, 2,3-dihydro-3,5 dihydroxy-6-methyl- exhibited the strongest binding affinity against EGFR (−5.4 kcal/mol), AKT1 (−6.5 kcal/mol), and BACE-1 (−5.1 kcal/mol), supported by stable hydrogen bonding and hydrophobic interactions within the active binding pockets. Molecular dynamics simulations demonstrated stable protein–ligand complex formation throughout the 100 ns simulation period, with favorable RMSD, RMSF, SASA, radius of gyration, hydrogen bonding, and potential energy profiles. Collectively, the findings suggest that 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- possesses promising multitarget neuroprotective potential by modulating inflammatory, apoptotic, and amyloidogenic pathways implicated in neurodegenerative disorders. Further experimental validation is required to confirm its therapeutic applicability.