Ferulic Acid as a Potential Drug for Neurological Disorder: An In silico Approach

Glycogen synthase kinase-3 (GSK-3) has been known to regulate various cellular and metabolic processes, including neuronal plasticity. Dysregulation of the GSK-3β isoform leads to the development of various neurological disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease. Thus, GSK-3β has gained major attention for therapeutic intervention in various neurological disorders. The present study aimed to explore natural derivatives of therapeutic value as potential inhibitors of GSK-3β for consideration in the treatment of neurological disorders. Using an In silico approach through virtual screening, molecular docking, and Molecular Dynamic (MD) simulation, we elucidate ferulic acid's binding interaction and affinity with GSK-3β residues. Our study revealed that ferulic acid (out of 545 phytochemicals from Mangifera indica) demonstrated effective inhibitory activity for GSK-3β. Interestingly, MD-simulation results showed that ferulic acid binds with three crucial amino acid residues of GSK-3β for modulating the activity. In addition, ferulic acid passed all Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME/Tox) parameters, paving the way for drug design and development targeting neurological disorders. Our findings provide the basis for development of Ferulic acid as a potential GSK-3β inhibitor.