Identification of Active Phytochemicals from Withania somnifera Against Alzheimer's Disease Through Molecular Docking Approach

Abstract

A large number of neurodegenerative diseases exist. Another such is Alzheimer’s disease (AD), a slow neurodegenerative disease that leads to reduced brain function when AChE activity is impaired. Instead of using Donepezil and Rivastigmine for Alzheimer’s treatment, it is advisable to come up with alternative therapies with fewer risks. Even though Withania somnifera (Ashwagandha) is known in Ayurveda medicine for protecting the brain, its relationship with AD targets is yet to be studied. The authors used in silico molecular docking to inspect the binding of nine active compounds from W. somnifera to human AChE (PDB: 4EY7) compared to commonly used reference drugs. A molecule with good binding affinity is solasodine, with a binding affinity of -8.2 kcal/mol. The outcomes from analyzing his solasodine were superior to the outcomes for donepezil and rivastigmine, each valuing 6.9 and 5.6 kcal/mol of binding. Additionally, Serge’s research revealed that scopolamine does not compete for binding at GABA’s site since it connected to the peripheral anionic site PAS and formed bonds with LEU308 by becoming hydrophobic and with ILE316 via a hydrogen bond. Withasomnine and scopoletin, two significant binders, interacted with the central TYR503 and ASN533 using strong forces. According to Lipinski’s rule of five, each top ligand appeared to have positive properties related to drug absorption and permeability through the barrier. The study demonstrates that W. somnifera is a helpful source for AD treatments using multiple targets and solasodine is suitable for additional studies in the lab and in experiments on animals.