Computational Simulations Reveal the Synergistic Action of Phytochemicals of Morus alba to Exert Anti-Alzheimer Activity via Inhibition of Acetylcholinesterase and Glycogen Synthase Kinase-3β

Paul A., Zothantluanga J. H., Rakshit G., ÇELİK İ., Rudrapal M., Zaman M. K.

Polycyclic Aromatic Compounds, vol.44, no.5, pp.3476-3500, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 5
  • Publication Date: 2024
  • Doi Number: 10.1080/10406638.2023.2236759
  • Journal Name: Polycyclic Aromatic Compounds
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Computer & Applied Sciences, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Page Numbers: pp.3476-3500
  • Keywords: Morus alba, anti-Alzheimer, neuroprotective, phytochemicals, in-silico
  • Erciyes University Affiliated: Yes

Abstract

Morus alba Linn. is a popular medium-sized tree with a potent neuroprotective activity such as anti-Alzheimer. To date, it is not known which phytocompound of M. alba exerts anti-Alzheimer activity. Therefore, the present study was aimed to identify the phytochemicals of M. alba responsible for the anti-Alzheimer activity by targeting proteins such as acetylcholinesterase (AChE) and glycogen synthase kinase-3 beta (GSK-3β) that are associated in the pathogenesis of Alzheimer disease (AD). Molecular docking, molecular dynamics (MD) simulations and MM-GBSA calculations were performed for the study. Phytocompounds with code 32, 41, 67, and 70 showed the best glide gscore against AchE and GSK-3β. All these phytocompounds interacted with multiple crucial amino acids present at the active binding site of the proteins through conventional hydrogen bonds and hydrophobic interactions. MD simulations of 100 ns revealed stable conformation for all protein-ligand complexes. Based on the computational findings, we conclude that M. alba’s phytoconstituents (32, 41 67, and 70) exerts anti-Alzheimer potential by inhibiting AChE and GSK-3β.