Therapeutic Potential of Morin in Alzheimer's Disease: An Integrated Network Pharmacology, Molecular Docking, ADMET, and Molecular Dynamics Study

ABSTRACT Neurotherapeutics that target kinases are necessary because Alzheimer's disease (AD) is characterized by a persistent decrease in cognitive function that is linked to amyloid‐β accumulation and tau hyperphosphorylation. This research highlights the dietary flavonoid morin as a potential therapeutic agent through a comprehensive integrated approach that incorporates network pharmacology, molecular docking, long‐timescale molecular dynamics (MD), density‐functional theory (DFT), and in silico ADMET profiling. With a focus on the significance of GSK‐3β in AD, network pharmacology successfully connected Morin's predicted targets with genes relevant to AD by highlighting important kinase hubs using the STRING/Cytoscape and DAVID/ShinyGO tools. Within the ATP site of GSK‐3β (PDB: 8FF8), Morin showed a competitive binding score of around −8.8 kcal/mol in docking tests. Along with contact with Gly185, Asp200, Lys85, and Phe67, it formed crucial connections with residues like Val135 and Asp133. The stability of the docking posture was validated by molecular dynamics simulations conducted over 1000 ns. The ligand RMSD averaged 3.58 ± 0.92 Å, whereas the protein Cα RMSD stabilized at 2.34 ± 0.31 Å, indicating a stable kinase conformation and a consistent contact network. The DFT study provides electronic descriptors that show how well Morin works in π‐stacking and hydrogen‐bonding interactions, which are crucial for its role in kinase pockets. Morin has problems with blood–brain barrier (BBB) permeability. However, ADMET profiling indicates that it is feasible for oral administration with minimal Geno and cardiotoxic hazards. Therefore, the need for CNS‐targeted delivery methods, including lipid carriers, prodrugs, or intranasal routes, is highlighted. The combination of network pharmacology, docking fidelity, MD stability, good electrical properties, and a respectable ADMET profile makes Morin a viable option for GSK‐3β inhibition in AD. Research is underway to support its therapeutic potential via experimental validation using CNS‐targeted formulation studies, neuroprotective assessments, and enzyme inhibition experiments.