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Cited by 273Phytochemicals and Antioxidant ActivitiesMedicinal Plants and NeuroprotectionAlzheimer's disease research and treatments

Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development

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Grabska-Kobyłecka, Izabela, Szpakowski, Piotr, Król, Aleksandra, Książek-Winiarek, Dominika, Kobyłecki, Andrzej, Głąbiński, Andrzej, Nowak, Dariusz·2023·Nutrients
DOI 10.3390/nu15153454PMC PMC10420887
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Abstract

It is well known that neurodegenerative diseases’ development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of mitochondrial function, cellular damage, and dysfunction of DNA repair systems. The increased consumption of antioxidants can postpone the development of these disorders and improve the quality of patients’ lives who have already been diagnosed with neurodegenerative diseases. Prolonging life span in developed countries contributes to an increase in the incidence ratio of chronic age-related neurodegenerative disorders, such as PD (Parkinson’s disease), AD (Alzheimer’s disease), or numerous forms of age-related dementias. Dietary supplementation with neuroprotective plant-derived polyphenols might be considered an important element of healthy aging. Some polyphenols improve cognition, mood, visual functions, language, and verbal memory functions. Polyphenols bioavailability differs greatly from one compound to another and is determined by solubility, degree of polymerization, conjugation, or glycosylation resulting from chemical structure. It is still unclear which polyphenols are beneficial because their potential depends on efficient transport across the BBB (blood-brain barrier), bioavailability, and stability in the CNS (central nervous system). Polyphenols improve brain functions by having a direct impact on cells and processes in the CNS. For a direct effect, polyphenolic compounds must be able to overcome the BBB and accumulate in brain tissue. In this review, the latest achievements in studies (animal models and clinical trials) on the effect of polyphenols on brain activity and function are described. The beneficial impact of plant polyphenols on the brain may be summarized by their role in increasing brain plasticity and related cognition improvement. As reversible MAO (monoamine oxidase) inhibitors, polyphenols are mood modulators and improve neuronal self-being through an increase in dopamine, serotonin, and noradrenaline amounts in the brain tissue. After analyzing the prohealth effects of various eating patterns, it was postulated that their beneficial effects result from synergistic interactions between individual dietary components. Polyphenols act on the brain endothelial cells and improve the BBB’s integrity and reduce inflammation, thus protecting the brain from additional injury during stroke or autoimmune diseases. Polyphenolic compounds are capable of lowering blood pressure and improving cerebral blood flow. Many studies have revealed that a nutritional model based on increased consumption of antioxidants has the potential to ameliorate the cognitive impairment associated with neurodegenerative disorders. Randomized clinical trials have also shown that the improvement of cognitive functions resulting from the consumption of foods rich in flavonoids is independent of age and health conditions. For therapeutic use, sufficient quantities of polyphenols must cross the BBB and reach the brain tissue in active form. An important issue in the direct action of polyphenols on the CNS is not only their penetration through the BBB, but also their brain metabolism and localization. The bioavailability of polyphenols is low. The most usual oral administration also conflicts with bioavailability. The main factors that limit this process and have an effect on therapeutic efficacy are: selective permeability across BBB, gastrointestinal transformations, poor absorption, rapid hepatic and colonic metabolism, and systemic elimination. Thus, phenolic compounds have inadequate bioavailability for human applications to have any beneficial effects. In recent years, new strategies have been attempted in order to exert cognitive benefits and neuroprotective effects. Converting polyphenols into nanostructures is one of the theories proposed to enhance their bioavailability. The following nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as neuroprotectors. Perhaps some modification of the chemical structure of a given polyphenol may increase its neuroprotective activity and transportation through the BBB. However, numerous questions should be answered before developing neuroprotective medications based on plant polyphenols.

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  • Polyphenols such as resveratrol, curcumin, and epigallocatechin gallate exert antioxidant and anti-inflammatory effects while modulating amyloid and tau pathways.

    “Polyphenols such as resveratrol, curcumin, and epigallocatechin gallate exert antioxidant and anti-inflammatory effects while modulating amyloid and tau pathways [182].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [182]

    Section 2.2 reports antioxidant and anti-inflammatory activity among dietary polyphenols and describes curcumin and resveratrol affecting Aβ aggregation or tau phosphorylation. Section 3 reports that EGCG suppresses microglial inflammation, but our copy does not link EGCG to amyloid or tau modulation. The claim therefore overextends the pathway finding to all three named examples. (LLM, conf=0.84)

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Authors
Grabska-Kobyłecka, I., Szpakowski, P., Król, A., Książek-Winiarek, D., Kobyłecki, A., Głąbiński, A., & Nowak, D.
Affiliations
  • Medical University of Lodz (PL)
  • Department of Neurology and Stroke, Medical University of Lodz, Zeromskiego 113 Street, 90-549 Łódź, Poland
  • Copernicus Memorial Hospital (PL)
Corresponding author
  • Grabska-Kobyłecka, Izabela
  • Nowak, Dariusz
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2023-08-04
Volume
15
Issue
15
Pages
3454
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu15153454
PMC
PMC10420887
OpenAlex
W4385577667
Cited by
273
References
17
Citations by year
2026: 95 · 2025: 114 · 2024: 59 · 2023: 5
FWCI
5.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
plant polyphenols, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, blood-brain barrier, bioavailability, oxidative stress, neuroinflammation, neuroplasticity, cognitive function, monoamine oxidase inhibition, flavonoids, dietary antioxidants, healthy aging, brain endothelial cells, cerebral blood flow, dietary habits, neuroprotection, mitochondrial dysfunction, DNA repair
MeSH terms
Animals, Antioxidants, Humans, Inflammation, Neurodegenerative Diseases, Endothelial Cells, Polyphenols

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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.

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