Abstract

COMPUTATIONAL EVALUATION OF ASHWAGANDHA COMPOUNDS AGAINST ALZHEIMER’S DISEASE

Md. Tanweer Kausar*, Priyanka Shrivastava, Dr. Satish Kumar Sarankar

Abstract

Alzheimer’s disease involves several processes, and compounds acting at more than one relevant target warrant investigation. The present study examines twelve constituents of Withania somnifera against acetylcholinesterase, butyrylcholinesterase, beta secretase 1, glycogen synthase kinase 3 beta and cyclooxygenase 2. The reported dissertation dataset was evaluated using molecular docking scores, pharmacokinetic predictions and target network information. Fifteen compounds, including three reference drugs, provided 75 docking combinations. Withaferin A and Ashwagandhanolide shared the lowest butyrylcholinesterase score of −11.725 kcal/mol. Withanolide D gave the lowest beta secretase 1 score of −10.670 kcal/mol. Sitoindoside IX ranked first among the phytochemicals against the remaining three targets. Six aglycones were reported with zero Lipinski violations, whereas none of the phytochemicals had a favourable reported brain penetration prediction. Withaferin A, Withanolide D, Sitoindoside IX and Ashwagandhanolide warrant further evaluation, with Withanolide A retained as a comparator. The findings provide a preliminary basis for compound selection. Unresolved input and validation records limit reproducibility, and experimental studies are required to establish inhibition, exposure and biological activity.

Keywords: Withania somnifera; Alzheimer’s disease; molecular docking; butyrylcholinesterase; withanolides; pharmacokinetics.