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Antioxidants
Special Issues
Role of Natural Antioxidant Compounds in Slowing Neurodegeneration
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Role of Natural Antioxidant Compounds in Slowing Neurodegeneration

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2605

Special Issue Editor

Dr. Jessica Maiuolo

E-Mail Website
Guest Editor
Laboratory of Pharmaceutical Biology, IRC-FSH Center, Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
Interests: plant extract; polyphenols; neurodegeneration; human health; microbiota
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegeneration is a pathological process causing progressive neuronal damage, potentially leading to cell death. Neurodegenerative diseases share a common feature: neurodegeneration, leading to functional, cognitive, and motor impairments. There are many causes responsible for neurodegeneration, including oxidative stress, misfolded proteins, neuroinflammation, mitochondrial dysfunction, brain injury, autophagy, and gene mutations. Among these, oxidative stress and inflammation appear to be a common denominator of neurodegeneration. Currently, no drug is known to cure neurodegenerative diseases definitively. Some lifestyles may help reduce the development of these diseases; for example, a balanced diet is associated with a lower risk of some neurodegenerative conditions. A diet focusing on fruits, vegetables, monounsaturated fats, fish, whole grains, legumes, and nuts, with moderate alcohol intake and limited red meat, dairy, saturated fats, and refined cereals, may help protect the brain.

Phytochemicals, bioactive compounds in plants, show promising therapeutic potential for many human diseases by possibly preventing or treating various pathological aspects. These substances often exhibit antioxidant and anti-inflammatory effects in the brain, activating protective mechanisms.

This Special Issue is aimed at the following:

  • Researchers dealing with neurodegeneration and the development of natural compounds capable of slowing its progression;
  • Botanists describing an extract with protective properties for the brain;
  • Neurologists who study the onset of neurodegenerative diseases and can propose non-pharmacological strategies to address them;
  • Researchers studying microbiota and the close gut–brain connection;
  • All scholars passionate about this topic.

Dr. Jessica Maiuolo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegeneration
  • neurodegenerative diseases
  • plant extracts
  • natural compounds
  • phytochemicals
  • polyphenols
  • gut-microbiota
  • gut–brain axis
  • brain and short-chain fatty acids

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Published Papers (3 papers)

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Research

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18 pages, 575 KB  
Article
Combined Fish Oil and Pine Bark Extract Supplementation Improves Short-Term Memory and the Antioxidant Status in Middle-Aged and Older Adults with Mild Cognitive Impairment: A Randomized Double-Blind, Parallel-Group Pilot Study
by Tse-Chia Hsiao, Cheng-Dien Hsu, Qian Xiao, Yi-Hsiu Chen, Yannick Piriou, Hitoshi Shirakawa and Suh-Ching Yang
Antioxidants 2026, 15(5), 588; https://doi.org/10.3390/antiox15050588 - 6 May 2026
Viewed by 430
Abstract
Mild cognitive impairment (MCI) represents an intermediate stage between normal cognitive function and dementia. Delaying the onset or progression of dementia has therefore become a key research priority. Although previous studies have examined the individual effects of fish oil or pine bark extract [...] Read more.
Mild cognitive impairment (MCI) represents an intermediate stage between normal cognitive function and dementia. Delaying the onset or progression of dementia has therefore become a key research priority. Although previous studies have examined the individual effects of fish oil or pine bark extract on cognitive decline, their findings remain inconclusive. In this study, we compared the effects of fish oil alone versus fish oil combined with pine bark extract on cognitive function and the oxidative status in patients with MCI. Participants aged 55–75 years with MCI were enrolled in a 24-week, double-blind, parallel-group trial, and they were randomly assigned to either a fish oil group (F group, n = 14), which received one fish oil capsule (350 mg eicosapentaenoic acid and 250 mg docosahexaenoic acid) and one placebo capsule, or a fish oil combined with pine bark extract group (F+P group, n = 14), which received one fish oil capsule and one pine bark extract capsule (100 mg). Compared to the baseline, the F group showed a significant decrease in Clinical Dementia Rating scores and a significant increase in Mini-Mental State Examination scores. In the subdomain analysis of the Cognitive Abilities Screening Instrument, the F group demonstrated a significant increase in the drawing score, whereas the F+P group showed a significant increase in the short-term memory score. Regarding the antioxidant status, compared to the baseline, the F group exhibited a significant increase in plasma thiobarbituric acid reactive substance (TBARS) levels and erythrocytic superoxide dismutase activity, whereas catalase (CAT) activity significantly decreased. After 24 weeks, plasma TBARS levels showed no significant change, while CAT activity was significantly higher in the F+P group than in the F group. These findings suggest that combined supplementation with fish oil and pine bark extract may be associated with potential improvements in short-term memory performance and antioxidant status in middle-aged and older adults with MCI, although the results should be interpreted cautiously. Full article
(This article belongs to the Special Issue Role of Natural Antioxidant Compounds in Slowing Neurodegeneration)
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20 pages, 2257 KB  
Article
The Significant Antioxidant Effect Exerted by Pomegranate (Punica granatum): The Hidden Polyphenols
by Rosamaria Caminiti, Valeria Mazza, Jessica Maiuolo, Federico Liuzzi, Francesca Oppedisano, Saverio Nucera, Salvatore Ragusa, Luigi Tucci, Giuseppe Trunfio, Lucia Carmela Passacatini, Sara Ilari, Ernesto Palma, Vincenzo Mollace and Carolina Muscoli
Antioxidants 2026, 15(3), 276; https://doi.org/10.3390/antiox15030276 - 24 Feb 2026
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Abstract
Background: Although the definition of dietary fibre is complex and constantly evolving, today we can identify it as “carbohydrate polymers with at least 10 monomeric units, which are not hydrolysed in the small intestine of humans”. In addition to the numerous and [...] Read more.
Background: Although the definition of dietary fibre is complex and constantly evolving, today we can identify it as “carbohydrate polymers with at least 10 monomeric units, which are not hydrolysed in the small intestine of humans”. In addition to the numerous and well-known benefits of dietary fibre for human health, our attention is drawn to its antioxidant properties, achieved through polyphenolic compounds linked to polysaccharide complexes. This study investigated the antioxidant effects of an extract from the fruit of Punica granatum (PUN), particularly rich in polyphenols, fibre, flavonoids, vitamins, organic acids, minerals, amino acids, and alkaloids. Furthermore, these effects were evaluated in two human nervous system cell lines under oxidative stress induced by hydrogen peroxide. Methodology: After examining the fibre composition, some polyphenols present in the extract were identified and quantified by HPLC. Furthermore, the antioxidant power of PUN was measured using the DPPH method, the chelating activity assay, the reducing power test, the ORAC method, the measurement of reactive oxygen species accumulation, the quantification of lipid peroxidation, and the detection of mitochondrial superoxide in cell cultures. Results: The results were consistent, and PUN demonstrated a strong antioxidant potential, justified not only by the high content of easily extractable polyphenols (EPPs) but also by a further addition of these more difficult to identify compounds (NEPPs), indicated as “hidden polyphenols”; therefore, the total polyphenol content in the extract resulted from the sum of EPPs + NEPPs (71 ± 7.9 + 55 ± 6.4 mg = 126 ± 14.3 mg gallic acid equivalent (GAE)/g dry weight). The fraction of hidden polyphenols could therefore explain a mechanism by which the fibre exerts an antioxidant effect. Another important result was achieved by the cell lines used, both of which were significantly protected by PUN following oxidative damage generated by a pro-oxidant treatment. However, astrocytes were found to be more responsive and sensitive than were human neurons. At the same time, PUN mitigated the effects of oxidative damage, and it could be hypothesised that this extract could be used to extinguish the A1 phenotype. Conclusions: We can conclude that the fibrous component of pomegranate is related to the antioxidant property exerted, and the neurodegeneration caused by oxidative stress could be slowed following the intake of Punica granatum. It is possible to identify the pomegranate as a “superfood” or “functional food”, with excellent nutritional characteristics and chemical composition. Full article
(This article belongs to the Special Issue Role of Natural Antioxidant Compounds in Slowing Neurodegeneration)
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Review

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17 pages, 2767 KB  
Review
Plasma Membrane Redox Failure Links COVID-19 Metabolic Stress to Ferroptotic Neurodegeneration
by Jaewang Lee, Hyosin Hwang and Dong-Hoon Hyun
Antioxidants 2026, 15(5), 572; https://doi.org/10.3390/antiox15050572 - 1 May 2026
Viewed by 362
Abstract
Oxidative stress and redox imbalance are central features of both age-related neurodegenerative disorders and the persistent neurological sequelae of coronavirus disease 2019. Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts neuronal redox homeostasis via mitochondrial dysfunction, iron dysregulation, [...] Read more.
Oxidative stress and redox imbalance are central features of both age-related neurodegenerative disorders and the persistent neurological sequelae of coronavirus disease 2019. Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts neuronal redox homeostasis via mitochondrial dysfunction, iron dysregulation, inflammatory signaling, and the depletion of pyridine nucleotide pools. In that context, ferroptosis provides a unifying mechanistic framework linking lipid peroxidation to progressive neuronal injury. This review proposes that neuronal vulnerability might depend not only on the oxidative burden itself but also on the failure of membrane-localized antioxidant defenses. Particular emphasis is placed on the plasma membrane redox system (PMRS), a membrane-associated quinone-reducing network that can support coenzyme Q redox cycling and constrain lipid radical propagation at the plasma membrane. Unlike canonical ferroptosis defense systems that rely predominantly on NADPH, components of the PMRS, particularly cytochrome b5 reductase, can also use NADH, conferring partial metabolic flexibility in conditions of redox stress. We further discuss how SARS-CoV-2-induced NAD+ depletion might progressively destabilize this membrane-proximal defense architecture, potentially lowering the ferroptotic threshold of vulnerable neurons. Finally, we outline therapeutic strategies that might reinforce PMRS-dependent membrane redox control through NRF2 activation, NAD+ restoration, coenzyme Q-centered interventions, and modulation of iron-catalyzed lipid oxidation. Full article
(This article belongs to the Special Issue Role of Natural Antioxidant Compounds in Slowing Neurodegeneration)
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