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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: 31 October 2025 | Viewed by 52

Special Issue Editor


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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 (1 paper)

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Research

17 pages, 2439 KiB  
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 (registering DOI) - 30 Apr 2025
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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