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Nutrients
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Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases
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Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: 5 May 2026 | Viewed by 20674

Special Issue Editor

Dr. Francesca Pacifici

E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Interests: natural compounds; antioxidants; neurodegenerative disorders; aging; diabetes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are among the ten most prelevant causes of death worldwide, and they have the distinction of being the leading cause of illness and disability globally. Although therapeutic strategies have improved over the last decades, neurodegenerative disorders remain orphan illnesses, with no cure to halt their progression. Several pharmacological and nutritional approaches have been proposed to alleviate symptoms and/or delay their progression. In particular, scientists are focusing their attention on natural phytochemicals, which have been found to be less toxic compared to proposed drugs. Numerous studies have demonstrated the significant effects of phytochemicals on reversing age-related cognitive decline. These benefits are mainly mediated by the antioxidant and anti-inflammatory properties of phytochemicals, which can promote the release of neurotrophins and induce neuronal regeneration and neuroprotection.

Considering all this evidence, this Topic aims to provide an in-depth exploration of a variety of natural phytochemicals in neurodegenerative disorders

Dr. Francesca Pacifici
Guest Editor

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Keywords

  • natural compounds
  • polyphenols
  • dietary phytochemicals
  • natural antioxidants
  • neuroprotection

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Published Papers (5 papers)

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Research

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18 pages, 6476 KB  
Article
Research on the Protective Effects and Mechanisms of Gallic Acid Against Cognitive Impairment Induced by Chronic Sleep Deprivation
by Xiangfei Zhang, Jingwen Cui, Jing Sun, Fengzhong Wang, Bei Fan and Cong Lu
Nutrients 2025, 17(20), 3204; https://doi.org/10.3390/nu17203204 - 12 Oct 2025
Cited by 2 | Viewed by 1203
Abstract
Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, [...] Read more.
Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
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16 pages, 4019 KB  
Article
Neuroprotective Effects of a Combination of Dietary Trans-Resveratrol and Hesperidin Against Methylglyoxal-Induced Neurotoxicity in a Depressive Amnesia Mouse Model
by Seon-Hyeok Kim, Seong-Min Hong, Eun-Ji Ko, Min-Jeong Park, Ji-Youn Kim and Sun-Yeou Kim
Nutrients 2025, 17(9), 1548; https://doi.org/10.3390/nu17091548 - 30 Apr 2025
Cited by 3 | Viewed by 1537
Abstract
Background: Methylglyoxal (MGO), a reactive dicarbonyl compound, has been implicated in the formation of advanced glycation end-products (AGEs) and neuronal dysfunction. This study investigated the neuroprotective effects of the combination of trans-resveratrol and hesperidin (tRES-HESP) against MGO-induced neurotoxicity, focusing on memory dysfunction and [...] Read more.
Background: Methylglyoxal (MGO), a reactive dicarbonyl compound, has been implicated in the formation of advanced glycation end-products (AGEs) and neuronal dysfunction. This study investigated the neuroprotective effects of the combination of trans-resveratrol and hesperidin (tRES-HESP) against MGO-induced neurotoxicity, focusing on memory dysfunction and depression-like behavior. Methods: Neuroblastoma 2a (N2a) cells were treated with MGO to induce neurotoxicity. The effects of tRES-HESP on cell viability, reactive oxygen species (ROS) production, apoptotic markers (BAX/Bcl 2 ratio, caspase 3 activity, and poly [ADP ribose] polymerase cleavage), and components of the glyoxalase system (glyoxalase-1, glyoxalase- 2, and receptors for AGEs) were assessed. The activation of the Kelch-like ECH-associated protein 1/Nuclear factor erythroid-2-related factor 2/Heme oxygenase-1 (Keap1/Nrf2/HO-1) pathway was also evaluated. In vivo, mice with MGO-induced depressive amnesia were treated with tRES-HESP (200 mg/kg) for eight weeks, and behavioral, biochemical, and histological assessments were performed. Results: tRES-HESP significantly reduced MGO-induced cytotoxicity, ROS production, and apoptosis in N2a cells. In addition, it restored the glyoxalase system and activated the Keap1/Nrf2/HO-1 pathway. In an in vivo model, tRES-HESP improved memory and depression-like behaviors, reduced cortisol and interleukin (IL)-6 levels, increased IL-10 levels, and lowered the expression of amyloid precursor protein and amyloid beta. Furthermore, tRES-HESP protected CA2/3 hippocampal subregions from MGO-induced damage. tRES-HESP exhibited neuroprotective effects through antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. Conclusions: Our results suggest that tRES-HESP is a potential dietary supplement for preventing cognitive decline and depression, particularly in neurodegenerative conditions such as Alzheimer’s disease. Further studies are required to assess its clinical relevance and efficacy in the human population. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
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Review

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42 pages, 989 KB  
Review
The Neuroprotective Role of Curcumin: From Molecular Pathways to Clinical Translation—A Narrative Review
by Andrea Lehoczki, Mónika Fekete, Tamás Jarecsny, Virág Zábó, Ágnes Szappanos, Tamás Csípő, Ágnes Lipécz, Dávid Major, Vince Fazekas-Pongor, Péter Varga and János Tamás Varga
Nutrients 2025, 17(17), 2884; https://doi.org/10.3390/nu17172884 - 6 Sep 2025
Cited by 3 | Viewed by 7390
Abstract
Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and post-stroke cognitive impairment (PSCI), represent an escalating global health and economic challenge. In the quest for disease-modifying interventions, natural polyphenols—most notably curcumin, the principal bioactive compound of Curcuma longa—have attracted considerable interest due [...] Read more.
Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and post-stroke cognitive impairment (PSCI), represent an escalating global health and economic challenge. In the quest for disease-modifying interventions, natural polyphenols—most notably curcumin, the principal bioactive compound of Curcuma longa—have attracted considerable interest due to their pleiotropic neuroprotective effects. This narrative review critically synthesizes findings from a selection of peer-reviewed articles published between 2000 and 2025, chosen for their relevance to curcumin’s molecular mechanisms and translational potential. Curcumin’s complex chemical structure confers antioxidant, anti-inflammatory, and epigenetic modulatory properties; however, its clinical application is limited by poor oral bioavailability. Mechanistically, curcumin attenuates oxidative stress and suppresses key inflammatory mediators, including nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Additionally, it modulates apoptosis, inhibits amyloid-beta aggregation, and enhances cellular quality control processes such as autophagy and mitophagy, while upregulating neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Preclinical studies employing rodent models of AD, PD, and ischemic stroke have demonstrated curcumin’s dose-dependent neuroprotective efficacy, with improved outcomes observed using nanoparticle-based delivery systems. Early-phase clinical trials further support curcumin’s favorable safety profile and potential cognitive benefits, although challenges remain regarding pharmacokinetics, formulation standardization, and therapeutic reproducibility. Future directions include the development of advanced drug delivery platforms, combinatory therapeutic regimens, and personalized medicine approaches integrating curcumin within multifaceted neurotherapeutic strategies. Collectively, this narrative review highlights curcumin as a promising multi-targeted candidate for combating neurodegenerative diseases, while emphasizing the need for further translational and clinical validation. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
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32 pages, 1902 KB  
Review
The Neuroprotective Potential of Ocimum Plant Species: Seasoning the Mind with Sweet and Holy Basil
by Alexandru Vasincu, Răzvan-Nicolae Rusu, Daniela-Carmen Ababei, Delia Bulea, Oana Dana Arcan, Ioana Mirela Vasincu, Sorin Beșchea Chiriac, Ionuț-Răducu Popescu, Walther Bild and Veronica Bild
Nutrients 2025, 17(17), 2877; https://doi.org/10.3390/nu17172877 - 5 Sep 2025
Viewed by 3453
Abstract
Neurodegenerative diseases (NDs) encompass a group of chronic conditions, characterized by neuronal losses in large areas of the brain, leading to cognitive and behavioral impairments. Alzheimer’s Disease (AD), the most common form of dementia, is a progressive ND, characterized by the accumulation of [...] Read more.
Neurodegenerative diseases (NDs) encompass a group of chronic conditions, characterized by neuronal losses in large areas of the brain, leading to cognitive and behavioral impairments. Alzheimer’s Disease (AD), the most common form of dementia, is a progressive ND, characterized by the accumulation of amyloid β and tau protein, entails cognitive decline, neuroinflammation, mitochondrial dysfunction, and blood–brain barrier impairment, with oxidative stress playing a critical role in its pathogenesis. To date, the available pharmacotherapy has shown limited efficacy, and multitarget activity of plant-derived neuroprotective bioactive compounds is currently in focus. This review synthesizes experimental evidence regarding Ocimum species with neuroprotective potential in AD, particularly Ocimum sanctum and Ocimum basilicum. These plants are rich in bioactive compounds including polyphenols, flavonoids, essential oils, and triterpenoids that synergistically scavenge reactive oxygen/nitrogen species, upregulate endogenous antioxidant enzymes (SOD, CAT, and GPx), and reduce lipid peroxidation. Furthermore, these extracts have demonstrated the ability to decrease β-amyloid accumulation and tau protein levels, key pathological features of AD. Even though additional research is required to fully assess their potential as therapeutic agents for NDs, by diving into the specific mechanisms through which they improve neurodegenerative processes, important steps can be made towards this endpoint. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
27 pages, 720 KB  
Review
Associations of the MIND Diet with Human Health Outcomes: A Scoping Review
by Katherine Hope Morgan, Michelle Lanphere Lee, Cristina S. Barroso, Joel G. Anderson, Shelley Lott, Danielle Reth, Chelsea Horn and Melanie Dixson
Nutrients 2025, 17(16), 2687; https://doi.org/10.3390/nu17162687 - 20 Aug 2025
Cited by 1 | Viewed by 6377
Abstract
The MIND diet was designed as an intervention to delay neurodegeneration and has been explored by systematic reviews for associations with cognition and, more recently, cardiometabolic disease. Comparatively less is known about how the MIND diet is associated with other health outcomes (e.g., [...] Read more.
The MIND diet was designed as an intervention to delay neurodegeneration and has been explored by systematic reviews for associations with cognition and, more recently, cardiometabolic disease. Comparatively less is known about how the MIND diet is associated with other health outcomes (e.g., all-cause mortality, anxiety, insomnia). This scoping review included studies exploring associations between the MIND diet and health outcomes other than cognition and cardiometabolic disease. Online databases were used to identify 4090 studies published between January 2015 and April 2024, from which 47 publications were included for review. Associations between the MIND diet and health outcomes were assessed as either favorable, unfavorable, or having no statistically significant association. Overall, 47 studies were included in this scoping review, 46 were observational, and several were conducted in large, established cohort studies. Across the 47 studies, 18 different topics were explored. Higher adherence to the MIND diet was mostly associated with favorable health outcomes (65%), while roughly one-third (33%) of studies found no statistically significant associations. One study, in Italy, found that increased adherence to the MIND diet was associated with increased exposure to cadmium, a heavy metal. In populations that may benefit from the MIND diet, we recommend additional observational and exploratory studies to identify health associations. Studies exploring educational interventions would help to identify facilitators and barriers to adopting the MIND diet. This scoping review provides some evidence that higher adherence to the MIND diet is associated with risk reduction for many diseases. Further research on environmental exposures (e.g., cadmium) and other deleterious substances absorbed by food crops will be crucial as we strive to enhance health and food security through plant-rich dietary patterns. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
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