From plants to potential therapeutics: exploring neuroprotective properties against Alzheimer’s disease through molecular docking and MD simulations

Abstract

Background: Alzheimer’s disease (AD) is a major global health concern, characterized by the accumulation of abnormal protein aggregates that cause cognitive decline. This study explores bioactive compounds from tra ditional medicinal plants as potential therapeutic candidates for AD treatment.

Methods: A total of 39 phytochemicals from Withania somnifera, Bacopa monnieri, Centella asiatica, and Cro cus sativus were investigated for their binding potential with AD-related enzymes, Acetylcholinesterase (AChE, PDB ID: 1B41) and β-Secretase (BACE-1, PDB ID: 1TQF), using molecular docking and molecular dynamics simulations. These compounds were further evaluated for drug-likeness and toxicity prediction.

Results: Retinoic acid (-9.2 kcal/mol) and Somniferine (-8.8 kcal/mol) demonstrated strong binding affinities with the target enzymes, as confirmed by molecular docking. Molecular dynamics simulations further vali dated the stability of these interactions. Additionally, drug-likeness and toxicity assessments highlighted the therapeutic potential of these compounds.

Conclusion: This study identifies Retinoic acid as a promising inhibitor of AChE and Somniferine as a novel in hibitor of BACE-1, suggesting their potential for treating Alzheimer’s disease. Further in-vivo studies and clini cal trials are recommended to confirm their efficacy and therapeutic application.

Keywords: Alzheimer’s disease, bioactive compounds, acetylcholinesterase, beta-secretase, molecular dock ing, molecular dynamics; toxicity