Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of β-amyloid (Aβ) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%-80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost-effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.
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Plant extracts may serve as valuable adjuncts or alternatives to conventional pharmacological treatments for Alzheimer's disease.
“The diverse mechanisms through which these plant extracts exert their effects—ranging from ChE inhibition to antioxidant activity—suggested that they may serve as valuable adjuncts or alternatives to conventional pharmacological treatments for AD [103,104].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [103]
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Shakil, S., Khan, R., Tabrez, S. S. M., Alam, Q., Jabir, N. R., Sulaiman, M. I., Greig, N. H., & Kamal, M. A. (2011) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152711798072365 · Cited by 19 · see citing works
Self-citationTello-Franco, V., Lozada-García, M. C., & Soriano-García, M. (2013) · Current Computer - Aided Drug Design · doi:10.2174/15734099113099990007 · Cited by 19 · see citing works
Akomolafe, S. F. (2017) · Journal of Food Biochemistry · doi:10.1111/jfbc.12401 · Cited by 19 · see citing works
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Exploration of Various Proteins for the Treatment of Alzheimer's Disease
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Acetylcholinesterase, Alpha-Glucosidase and Tyrosinase Inhibitors from Egyptian Propolis
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Specific Cholinesterase Inhibitors: A Potential Tool to Assist in Management of Alzheimer Disease
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Flagged first, then by citations
Cited by
Sorted by citations
Gao, L., Li, X., Meng, S., Ma, T., Wan, L., & Xu, S. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s235969 · Cited by 115 · see citing works
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Anti-Cholinesterase Combination Drug Therapy as a Potential Treatment for Alzheimer’s Disease
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ALNasser, M. N., Alboraiy, G. M., Alsowig, E. M., & Alqattan, F. M. (2025) · Brain Sciences · doi:10.3390/brainsci15020215 · Cited by 35 · see citing works
“The diverse mechanisms through which these plant extracts exert their effects—ranging from ChE inhibition to antioxidant activity—suggested that they may serve as valuable adjuncts or alternatives to conventional pharmacological treatments for AD [103,104].”
Treatment of Alzheimer’s disease by natural products
CHOUGLE, S., KUMAR, D., KHAN, A., ZEHRA, S., & ALİ, A. (2021) · Journal of Experimental and Clinical Medicine · doi:10.52142/omujecm.38.4.42 · Cited by 8 · see citing works
- Authors
- Jabir, N. R., Khan, F. R., & Tabrez, S.
- Affiliations
- King Abdulaziz University (SA)
- Corresponding author
- Tabrez, Shams
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2018-05-16
- Volume
- 24
- Issue
- 9
- Pages
- 753-762
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6489761
- OpenAlex
- W2803878064
- Cited by
- 187
- References
- 111
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 25 · 2023: 21 · 2022: 33 · 2021: 34 · 2020: 15 · 2019: 14 · 2018: 2 · 2017: 1
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- 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, cholinesterase inhibitors, polyphenols, cholinergic system, quercetin, resveratrol, curcumin, gallocatechin, cinnamic acid, caffeine, caffeic acid, natural compounds, amyloid-beta, tau hyperphosphorylation, neurofibrillary tangles, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Cholinesterase Inhibitors, Cholinesterases, Humans, Drug Delivery Systems, tau Proteins, Treatment Outcome, Polyphenols
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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