Exploring the diverse acetylcholinesterase inhibitory potential of girinimbine: insights from in vitro assays, molecular docking, and simulation studies

Taha MME 1 , Khalid A 2 , Elfatih F 3 , Mohan S 4 , Sukumaran SD 5 , Ul-Haq Z 6 Show all authors , Aljahdali IA 7 , Oraibi O 8 , Oraibi B 9 , Alfaifi HA 10 , Alzahrani AH 11 , Farasani A 12 , Jerah AA 13 , Babiker YOH 14 , Abdelwahab SI 4

Affiliations 

  • 1 Health Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia. [email protected]
  • 2 Health Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia. [email protected]
  • 3 Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P. O. Box 2404, Khartoum, Sudan. [email protected]
  • 4 Health Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia. [email protected]
  • 5 Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia. [email protected]
  • 6 Dr. Panjwani Center for Molecular Medicine & Drug Research, University of Karachi, Karachi 75530, Pakistan. [email protected]
  • 7 Department of Clinical Laboratory Sciences, Taif University, Taif, Saudi Arabia. [email protected]
  • 8 Internal Medicine Department, Faculty of Medicine, Jazan, Jazan University, Saudi Arabia. [email protected]
  • 9 Health Research Center, Jazan University, P.O. Box: 114, Jazan 45142, Saudi Arabia. [email protected]
  • 10 Pharmaceutical Care Administration (Jeddah Second Health Cluster), Ministry of Health, Jeddah, Saudi Arabia. [email protected]
  • 11 Department of Pharmacology and Toxicology, College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. [email protected]
  • 12 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan-45142, Saudi Arabia. [email protected]
  • 13 Department of Surgery, College of Medicine, Jazan University, Jazan, 45142 Saudi Arabia. [email protected]
  • 14 . [email protected]
Cell Mol Biol (Noisy-le-grand), 2024 Nov 24;70(10):154-160.
PMID: 39605111 DOI: 10.14715/cmb/2024.70.10.20

Abstract

The search for new treatments for Alzheimer's disease (AD) has led to the exploration of plant-based drugs as potential options. Acetylcholinesterase (AChE) inhibitors are widely used as anti-AD medications. This study aimed to investigate the inhibitory mechanism of girinimbine, a constituent of Murraya koenigii, on AChE. AChE inhibition was assessed by in vitro experiments using the modified Ellman method, as well as in silico molecular docking and molecular dynamic simulation. The results were compared to those of the well-known anti-AChE agents tacrine and propidium iodide. Girinimbine, propidium, and tacrine at concentrations of 3.8X10-5M, 1.1x10-5M, and 6.1x10-7M showed percentages of inhibition percentages of 35.6%, 28.2%, and 76.6%, respectively. The docking and molecular dynamics simulation analyses indicated that girinimbine exhibited a higher binding affinity to AChE compared to propidium and tacrine. This finding was further confirmed by the docking, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of rotation analyses. In conclusion, M. koenigii girinimbine shows promise as an acetylcholinesterase inhibitor for Alzheimer's disease. Further research, including in vivo studies and clinical trials, is needed to explore its potential as a plant-based drug candidate for AD treatment.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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