Identification of potential lead compounds against BACE1 through in-silico screening of phytochemicals of Medhya rasayana plants for Alzheimer's disease management
Abstract
Alzheimer's disease is a progressive and irreversible neurodegenerative disease that accounts for 70-80% of dementia in the elderly. According to recent clinical data, the incidence of the disease is exponentially increasing with age. Beta-site amyloid precursor protein cleaving enzyme1 (BACE1) is an important molecule involved in the pathogenesis of Alzheimer's disease due to its early role in the amyloid cascade. Cleavage of amyloid precursor protein by BACE1 is the rate-limiting step leading to the production and aggregation of amyloid-beta plaques. A number of natural products are being identified as non-competitive BACE1 inhibitors. In Ayurveda, Medhya rasayana is a group of medicinal herbs, specifically used for managing neurological disorders and is known to be effective in improving cognitivity and intellect. This study aimed to analyze the pharmacological activity of bio-active compounds in Medhya rasayana plants against BACE1, employing structure-based docking approach. 11 compounds out of 876 were identified as potential hits, based on docking scores, binding energies, and interactions with the critical residues of BACE1. Possible neurological activities of these compounds were predicted using PASS server. Out of the 11 compounds screened, two compounds, 'Convolidine' from the plant Convolvulus pleuricaulis Choisy and 'N-(4-hydroxybutyl) phthalimide' from Glycyrrhiza glabra satisfied the pharmacological parameters of Lipinski rule of filtering and ADMET prediction. The binding stability of these compounds against BACE1 was confirmed by molecular dynamic simulation and post dynamic MM/GBSA calculations. Detailed analysis of the interaction with the critical amino acids in the active site revealed the possible inhibitory potential of these compounds of medicinal plant origin against BACE1.
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Phytoactive compounds in Glycyrrhiza species inhibit BACE1.
“Furthermore, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), a significant molecule involved in the etiology of AD, has been reported to be inhibited by the phytoactive compounds present in Glycyrrhiza species.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [71]
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- Authors
- Nadh, A. G., Revikumar, A., Sudhakaran, P. R., & Nair, A. S.
- Affiliations
- University of Kerala (IN)
- Rajiv Gandhi Centre for Biotechnology (IN)
- Corresponding author
- Nadh, Anuroopa G.
- Venue
- Computers in Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 145
- Pages
- 105422
- ISSN
- 0010-4825 (ISSN-L)
- OpenAlex
- W4220667983
- Cited by
- 22
- References
- 61
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Computers in Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- Alzheimer's disease, BACE1 inhibition, Medhya Rasayana, Ayurvedic medicinal plants, phytochemicals, licorice, amyloid-beta, structure-based virtual screening, molecular docking, molecular dynamics simulation, MM-GBSA binding free energy, ADMET prediction, natural product drug discovery
- MeSH terms
- Aged, Alzheimer Disease, Humans, Lead, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Neurodegenerative Diseases, Amyloid Precursor Protein Secretases, Molecular Docking Simulation, Phytochemicals
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