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Nutrients
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The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease
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The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease

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

Deadline for manuscript submissions: 30 April 2025 | Viewed by 8202

Special Issue Editors

Dr. Irene Cantarero-Carmona

E-Mail Website
Guest Editor
Department of Morphological and Sociosanitary Sciences, University of Cordoba, Cordoba, Spain
Interests: preclinical studies; innervation; regeneration; histology; muscle damage
Dr. Carmen Del Río Mercado

E-Mail Website
Guest Editor
Neurovascular Lab, Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Seville, Spain
Interests: neuroprotectancts; preclinical studies; drug discovery; stroke; neurovascular; nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bioactive compounds have been described as counteracting many of the pathological processes associated with neurodegeneration, given their antioxidant, anti-inflammatory, and neurotransmitter-modulating effects, among others. Therefore, it is not surprising that bioactive compounds have been suggested to play a role in neuroprotection and the management of neurodegenerative diseases.

These substances are often obtained from natural sources such as plants, fruits, or vegetables, and incorporating bioactive compounds into diets or as supplements offers a promising avenue for supporting brain health and function. However, more research is needed to fully understand their mechanisms of action and develop effective preventive and therapeutic strategies for neurodegeneration.

This Special Issue aims to gather recent knowledge on the effects of bioactive compounds in neuroprotection and their role in modulating neurodegenerative diseases. It is an exciting opportunity to highlight recent advances in this critical area of research. Original research articles (preclinical and human studies) and comprehensive reviews are welcome.

Dr. Irene Cantarero-Carmona
Dr. Carmen Del Río Mercado
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Nutrients is an international peer-reviewed open access semimonthly 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

  • neurodegenerative diseases
  • bioactive compounds
  • neuroprotection
  • food supplement

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Published Papers (6 papers)

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Research

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20 pages, 577 KiB  
Article
Evaluating the Clinical Impact of a Polyphenol-Rich Extract from Salicornia ramosissima on Patients with Transient Ischemic Attack and Minor Stroke
by Ana M. Nájar, Cristina López Azcárate, Carmen Domínguez Ruiz, David Núñez-Jurado, Reyes de Torres, Reyes López, Miriam Camino-Moya, Eleonora Magni, Emilio Montero-Ramirez, Antonio Bocero, Álvaro Laviana, Teresa Busquier Cerdán, Antonio León, Carmen del Rio, Joan Montaner and Soledad Pérez-Sánchez
Nutrients 2024, 16(24), 4307; https://doi.org/10.3390/nu16244307 - 13 Dec 2024
Cited by 1 | Viewed by 1153
Abstract
Transient ischemic attack (TIA) is a well-established risk factor for future strokes, making interventions that target recovery and vascular risk crucial. This study aimed to assess the safety and clinical effects of a polyphenol-rich Salicornia ramosissima extract in post-TIA patients. A randomized, triple-blind, [...] Read more.
Transient ischemic attack (TIA) is a well-established risk factor for future strokes, making interventions that target recovery and vascular risk crucial. This study aimed to assess the safety and clinical effects of a polyphenol-rich Salicornia ramosissima extract in post-TIA patients. A randomized, triple-blind, placebo-controlled trial was conducted with participants who had a history of TIA or minor stroke and who received 1 g of Salicornia extract or placebo over 11 months. Biochemical analyses, neuropsychological assessments (MOCA test), and gait and aerobic performance tests were conducted at the beginning and the end of the study. A total of 118 individuals were screened, with 80 finally included. Importantly, no significant adverse events were reported throughout the study. A neurological analysis showed an improvement in MOCA scores in patients treated with the Salicornia extract for 11 months. The treatment did not affect spatiotemporal gait parameters, but it significantly reduced blood pressure at baseline and after the aerobic performance test. Biochemically, both groups exhibited mild hyperhomocysteinemia at baseline; however, Salicornia treatment significantly lowered homocysteine levels, bringing them within the normal range. These findings highlight the safety of the Salicornia extract in patients at a high cerebrovascular risk and suggest it as a potential therapeutic option for managing vascular risk factors, such as hyperhomocysteinemia and hypertension. However, further studies are required to confirm the underlying mechanisms and explore broader clinical applications. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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19 pages, 2452 KiB  
Article
Optimization and Chemical Characterization of Extracts Obtained from Ferula persica var. latisecta Aerial Parts and Roots and Their Neuroprotective Evaluation
by Pouya Mohammadnezhad, Alberto Valdés and Alejandro Cifuentes
Nutrients 2024, 16(23), 4210; https://doi.org/10.3390/nu16234210 - 5 Dec 2024
Viewed by 1201
Abstract
Background/Objectives: The genus Ferula has been traditionally used for the treatment of various illnesses, but the potential of Ferula persica var. latisecta against different Alzheimer’s disease (AD) hallmarks has never been achieved. Methods: In this work, a pressurized liquid extraction (PLE) method was [...] Read more.
Background/Objectives: The genus Ferula has been traditionally used for the treatment of various illnesses, but the potential of Ferula persica var. latisecta against different Alzheimer’s disease (AD) hallmarks has never been achieved. Methods: In this work, a pressurized liquid extraction (PLE) method was optimized to extract F. persica L. aerial parts and roots. Four different solvents (water, ethanol, ethyl acetate (EtAc), and cyclopentyl methyl ether (CPME)) were first tested, and the extraction yield, total phenolic content, reactive oxygen species scavenging capacity, and acetylcholinesterase (AChE) inhibition activity were evaluated. Results: The results indicated that EtAc and CPME were the best solvents to be used, with the results obtained from the aerial parts being better than those obtained from the root samples. Thereafter, the PLE method was further optimized by combining these solvents in different percentages (100% EtAc, 100% CPME, and 50:50% (v/v) EtAc:CPME) and temperatures (50, 115, and 180 °C). Response surface methodology was then applied to analyze the data, and two optimum extraction conditions were obtained: EtAc:CPME (79:21%) at 180 °C for the aerial parts and 100% CPME at 180 °C for the roots. At these conditions, the total flavonoid content (TFC) and the inhibitory capacities against butyrylcholinesterase (BChE) and lipoxygenase (LOX) enzymes were also evaluated, indicating that the aerial part extracts had higher TFC and LOX inhibitory capacity than the root extracts but lower activity against BChE. The comprehensive LC/GC-MS chemical characterization allowed for the tentative identification of 222 compounds belonging to 66 chemical subclasses, the abundancies of which widely varied depending on the matrix and the extraction conditions used. Conclusions: The results obtained together with the application of advanced statistical analysis and molecular docking simulations suggested several sesquiterpenoids, such as selina-3,7(11)-diene, guaiol acetate, α-cyperone, and farnesyl acetate, as the molecules responsible of the in vitro results observed, with good neuroprotective potential against AD. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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27 pages, 3771 KiB  
Article
A Novel Supplement Consisting of Rice, Silkworm Pupae and a Mixture of Ginger and Holy Basil Improves Post-Stroke Cognitive Impairment
by Putthiwat Thongwong, Jintanaporn Wattanathorn and Wipawee Thukham-mee
Nutrients 2024, 16(23), 4144; https://doi.org/10.3390/nu16234144 - 29 Nov 2024
Viewed by 1073
Abstract
Backgrounds/Objectives: Despite the increasing importance of the condition of post-stroke cognitive impairment (PSCI), the current therapy efficacy is limited. Since oxidative stress and inflammation are targeted in anti-stroke therapy, we aimed to assess the protective effect against PSI of an orodispersible film loaded [...] Read more.
Backgrounds/Objectives: Despite the increasing importance of the condition of post-stroke cognitive impairment (PSCI), the current therapy efficacy is limited. Since oxidative stress and inflammation are targeted in anti-stroke therapy, we aimed to assess the protective effect against PSI of an orodispersible film loaded with silkworm pupae hydrolysate and a combined extract of holy basil and ginger (JP1), which show antioxidant, and anti-inflammation effects. Methods: Male Wistar rats (200–250 g) were administered JP1 at doses of 1, 10, and 100 mg/kg BW 45 min before a 6 h immobilization stress exposure for 14 days. Then, the right middle cerebral artery was permanently occluded (MCAO) and JP1 was continually administered for 21 days after MCAO. Spatial and non-spatial memory and the possible underlying mechanisms were also explored. Results: JP1 improved oxidative stress, inflammation, apoptosis, Erk signaling pathway, cholinergic function, and the growth of Lactobacillus and Bifidobacterium spp. in feces. These results suggest that JP1 improves PSCI, possibly involving the above mechanisms. Furthermore, serum corticosterone also decreased. Conclusions: Our results suggest that JP1 is a potential candidate for combating PSCI following exposure to stroke plus stress. However, a clear understanding of the precise active ingredient and the detailed mechanisms require further investigation. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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14 pages, 8907 KiB  
Article
Agathisflavone Modulates Reactive Gliosis After Trauma and Increases the Neuroblast Population at the Subventricular Zone
by Juliana Helena Castro e Silva, Francesca Pieropan, Andrea Domenico Rivera, Arthur Morgan Butt and Silvia Lima Costa
Nutrients 2024, 16(23), 4053; https://doi.org/10.3390/nu16234053 - 26 Nov 2024
Cited by 2 | Viewed by 989
Abstract
Background: Reactive astrogliosis and microgliosis are coordinated responses to CNS insults and are pathological hallmarks of traumatic brain injury (TBI). In these conditions, persistent reactive gliosis can impede tissue repopulation and limit neurogenesis. Thus, modulating this phenomenon has been increasingly recognized as potential [...] Read more.
Background: Reactive astrogliosis and microgliosis are coordinated responses to CNS insults and are pathological hallmarks of traumatic brain injury (TBI). In these conditions, persistent reactive gliosis can impede tissue repopulation and limit neurogenesis. Thus, modulating this phenomenon has been increasingly recognized as potential therapeutic approach. Methods: In this study, we investigated the potential of the flavonoid agathisflavone to modulate astroglial and microglial injury responses and promote neurogenesis in the subventricular zone (SVZ) neurogenic niche. Agathisflavone, or the vehicle in controls, was administered directly into the lateral ventricles in postnatal day (P)8-10 mice by twice daily intracerebroventricular (ICV) injections for 3 days, and brains were examined at P11. Results: In the controls, ICV injection caused glial reactivity along the needle track, characterised immunohistochemically by increased astrocyte expression of glial fibrillary protein (GFAP) and the number of Iba-1+ microglia at the lesion site. Treatment with agathisflavone decreased GFAP expression, reduced both astrocyte reactivity and the number of Iba-1+ microglia at the core of the lesion site and the penumbra, and induced a 2-fold increase on the ratio of anti-inflammatory CD206+ to pro-inflammatory CD16/32+ microglia. Notably, agathisflavone increased the population of neuroblasts (GFAP+ type B cells) in all SVZ microdomains by up to double, without significantly increasing the number of neuronal progenitors (DCX+). Conclusions: Although future studies should investigate the underlying molecular mechanisms driving agathisflavone effects on microglial polarization and neurogenesis at different timepoints, these data indicate that agathisflavone could be a potential adjuvant treatment for TBI or central nervous system disorders that have reactive gliosis as a common feature. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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25 pages, 5956 KiB  
Article
Anti-Neuroinflammatory Potential of Areca Nut Extract and Its Bioactive Compounds in Anthracene-Induced BV-2 Microglial Cell Activation
by Sakawrat Janpaijit, Monruedee Sukprasansap, Tewin Tencomnao and Anchalee Prasansuklab
Nutrients 2024, 16(17), 2882; https://doi.org/10.3390/nu16172882 - 28 Aug 2024
Cited by 3 | Viewed by 1896
Abstract
Particulate matter (PM2.5) containing polycyclic aromatic hydrocarbons (PAHs) is of considerable environmental importance worldwide due to its adverse effects on human health, which are associated with neurodegenerative diseases (NDDs). Areca catechu L. (AC) fruit is known to possess various pharmacological properties; [...] Read more.
Particulate matter (PM2.5) containing polycyclic aromatic hydrocarbons (PAHs) is of considerable environmental importance worldwide due to its adverse effects on human health, which are associated with neurodegenerative diseases (NDDs). Areca catechu L. (AC) fruit is known to possess various pharmacological properties; however, the anti-neuroinflammatory roles of AC on the suppression of PAH-induced neuroinflammation are still limited. Thus, we focused on the effects and related signaling cascades of AC and its active compounds against anthracene-induced toxicity and inflammation in mouse microglial BV-2 cells. Phytochemicals in the ethanolic extract of AC (ACEE) were identified using LC-MS, and molecular docking was conducted to screen the interaction between compounds and target proteins. Significant bioactive compounds in ACEE such as arecoline, (−)-epicatechin, and syringic acid were evinced through the LC-MS spectrum. The docking study revealed that (−)-epicatechin showed the highest binding affinities against NF-κB. For cell-based approaches, anthracene induced intracellular ROS, mRNA levels of TNF-α, IL-1β, and IL-6, and the release of TNF-α through enhancing JNK, p38, and NF-κB signaling pathways. However, the co-treatment of cells with ACEE or (−)-epicatechin could reverse those anthracene-induced changes. The overall study suggested that ACEE-derived bioactive compounds such as (−)-epicatechin may be developed as a potential anti-neuroinflammatory agent by preventing inflammation-mediated NDDs. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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Review

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21 pages, 938 KiB  
Review
Mechanistic and Therapeutic Insights into Flavonoid-Based Inhibition of Acetylcholinesterase: Implications for Neurodegenerative Diseases
by Natalia Cichon, Weronika Grabowska, Leslaw Gorniak, Maksymilian Stela, Piotr Harmata, Michal Ceremuga and Michal Bijak
Nutrients 2025, 17(1), 78; https://doi.org/10.3390/nu17010078 - 28 Dec 2024
Viewed by 1408
Abstract
Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial [...] Read more.
Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial role in cholinergic neurotransmission, is a key target in the treatment of cognitive impairments due to its function in acetylcholine hydrolysis. Natural polyphenolic compounds, particularly flavonoids, have demonstrated significant inhibition of AChE, positioning them as promising alternatives or adjuncts in neuropharmacology. This study specifically examines flavonoids such as quercetin, apigenin, kaempferol, and naringenin, investigating their inhibitory efficacy, binding mechanisms, and additional neuroprotective properties, including their antioxidant and anti-inflammatory effects. In vitro, in vivo, and in silico analyses reveal that these flavonoids effectively interact with both the active and peripheral anionic sites of AChE, resulting in increased acetylcholine levels and the stabilization of cholinergic signaling. Their mechanisms of action extend beyond mere enzymatic inhibition, as they also exhibit antioxidant and anti-amyloidogenic properties, thereby offering a multifaceted approach to neuroprotection. Given these findings, flavonoids hold considerable therapeutic potential as modulators of AChE, with implications for enhancing cognitive function and treating neurodegenerative diseases. Future studies should prioritize the enhancement of flavonoid bioavailability, evaluate their efficacy in clinical settings, and explore their potential synergistic effects when combined with established therapies to fully harness their potential as neurotherapeutic agents. Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in Neuroprotection and Neurodegenerative Disease)
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