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Dietary Polyphenols and Neuroprotection

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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: closed (31 August 2021) | Viewed by 41356

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Prof. Dr. Rui F. M. Silva

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Guest Editor

Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
Interests: neurosciences area, in the topics of neurobiology, neurotoxicology, neurodevelopment, and glial function associated with neurologic conditions and neurodegeneration; the most relevant area of intervention involves neuroprotection mechanisms, embracing the neuroprotective properties of food natural products and food-borne molecules, either introduced in the regular diet or as additives or medicines, by several cell and molecular mechanisms, beyond the traditional antioxidant properties described for food polyphenols
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Prof. Dr. Lea Pogačnik

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Co-Guest Editor

Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, SI-1000 Ljubljana, Slovenia
Interests: optimisation of extraction procedures and evaluation of bioactivities (antioxidant, antidiabetes, antimicrobial) in extracts of different plants (alien knotweed species - Fallopia japonica, F. sachalinensis, F. x bohemica; medicinal plants, tea, coffee, pomegranate, Aronia, onion leaves) and cyanobacteria (Spirulina) before and after the lactic acid fermentation; evaluation of brain accessibility and neuroprotection of different polyphenols (quercetin, EGCG, cyanidin-3-glucoside); simulation of digestion and evaluation of stability of polyphenols from different origin
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Special Issue Information

Dear Colleagues,

Polyphenols are naturally occurring molecules ubiquitous in plants. They are edible constituents of many food sources like wine, green tea, grapes, vegetables, red fruits, and coffee. Some of these molecules are also used as food supplements and proposed as nutraceutical medicinal drugs. Besides the recognized antioxidant and inflammatory properties, many studies using polyphenols have shown that they modulate several cellular functions and molecular pathways, with a significant impact on the prevention and treatment of various pathological conditions, like cancer, cardiovascular disorders, pollutant-induced cell damage, and also neurodegenerative diseases.

Neurodegenerative diseases are among the main causes of death worldwide and, in most of them, like Alzheimer’s or Parkinson’s, neurodegeneration occurs long before the onset of first symptoms, where a large population of brain neurons is already lost. Besides neurons, glial cells, like astrocytes and microglia, are involved in oxidative and neuroinflammatory pathological pathways, making them interesting targets for neuroprotective strategies. Polyphenols are promising candidates for those strategies, either as prophylactic substances or as therapeutic molecules. However, the health effects of polyphenols depend on the amount consumed and their bioavailability, raising some issues related to their safe use and overconsumption. We invite you to further explore all these issues, contributing with your prominent expertise to this Special Issue.

Prof. Dr. Rui F. M. Silva
Prof. Dr. Lea Pogačnik
Guest Editors

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Keywords

Food-born polyphenolic compounds
Neurodegeneration
Mechanisms of neuroprotection
Bioavailability
Safety

Related Special Issue

Dietary Polyphenols and Neuroprotection II in Antioxidants (2 articles)

Published Papers (10 papers)

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Editorial

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3 pages, 187 KiB

Open AccessEditorial

Neuroprotective Properties of Food-Borne Polyphenols in Neurodegenerative Diseases

by Rui F. M. Silva and Lea Pogačnik

Antioxidants 2021, 10(11), 1810; https://doi.org/10.3390/antiox10111810 - 15 Nov 2021

Cited by 1 | Viewed by 1191

Abstract

Fruits and vegetables are the richest source of polyphenols in the regular human diet [...] Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

Research

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14 pages, 5559 KiB

Open AccessArticle

Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives

by Andrius Sakalauskas, Mantas Ziaunys, Ruta Snieckute and Vytautas Smirnovas

Antioxidants 2021, 10(9), 1428; https://doi.org/10.3390/antiox10091428 - 07 Sep 2021

Cited by 5 | Viewed by 2160

Abstract

The increasing prevalence of amyloid-related disorders, such as Alzheimer’s or Parkinson’s disease, raises the need for effective anti-amyloid drugs. It has been shown on numerous occasions that flavones, a group of naturally occurring anti-oxidants, can impact the aggregation process of several amyloidogenic proteins and peptides, including amyloid-beta. Due to flavone autoxidation at neutral pH, it is uncertain if the effective inhibitor is the initial molecule or a product of this reaction, as many anti-amyloid assays attempt to mimic physiological conditions. In this work, we examine the aggregation-inhibiting properties of flavones before and after they are oxidized. The oxidation of flavones was monitored by measuring the UV-vis absorbance spectrum change over time. The protein aggregation kinetics were followed by measuring the amyloidophilic dye thioflavin-T (ThT) fluorescence intensity change. Atomic force microscopy was employed to image the aggregates formed with the most prominent inhibitors. We demonstrate that flavones, which undergo autoxidation, have a far greater potency at inhibiting the aggregation of both the disease-related amyloid-beta, as well as a model amyloidogenic protein—insulin. Oxidized 6,2′,3′-trihydroxyflavone was the most potent inhibitor affecting both insulin (7-fold inhibition) and amyloid-beta (2-fold inhibition). We also show that this tendency to autoxidize is related to the positions of the flavone hydroxyl groups. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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11 pages, 2275 KiB

Open AccessArticle

Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme

by Qiuchen Zheng, Micheal T. Kebede, Bethany Lee, Claire A. Krasinski, Saadman Islam, Liliana A. Wurfl, Merc M. Kemeh, Valerie A. Ivancic, Charles E. Jakobsche, Donald E. Spratt and Noel D. Lazo

Antioxidants 2021, 10(9), 1342; https://doi.org/10.3390/antiox10091342 - 25 Aug 2021

Cited by 5 | Viewed by 2593

Abstract

The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 that has been linked to the neurodegeneration in Alzheimer’s disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE’s activity for the clearance of Aβ42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE’s activity toward Aβ42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE’s activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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18 pages, 2369 KiB

Open AccessArticle

Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model

by Yuni Hong, Yun-Hyeok Choi, Young-Eun Han, Soo-Jin Oh, Ansoo Lee, Bonggi Lee, Rebecca Magnan, Shi Yong Ryu, Chun Whan Choi and Min Soo Kim

Antioxidants 2021, 10(6), 835; https://doi.org/10.3390/antiox10060835 - 24 May 2021

Cited by 8 | Viewed by 3085

Abstract

Neurodegenerative diseases are characterized by the progressive degeneration of the function of the central nervous system or peripheral nervous system and the decline of cognition and memory abilities. The dysfunctions of the cognitive and memory battery are closely related to inhibitions of neurotrophic factor (BDNF) and brain-derived cAMP response element-binding protein (CREB) to associate with the cholinergic system and long-term potentiation. Vitis vinifera, the common grapevine, is viewed as the important dietary source of stilbenoids, particularly the widely-studied monomeric resveratrol to be used as a natural compound with wide-ranging therapeutic benefits on neurodegenerative diseases. Here we found that ampelopsin A is a major compound in V. vinifera and it has neuroprotective effects on experimental animals. Bath application of ampelopsin A (10 ng/µL) restores the long-term potentiation (LTP) impairment induced by scopolamine (100 μM) in hippocampal CA3-CA1 synapses. Based on these results, we administered the ampelopsin A (10 ng/µL, three times a week) into the third ventricle of the brain in C57BL/6 mice for a month. Chronic administration of ampelopsin A into the brain ameliorated cognitive memory-behaviors in mice given scopolamine (0.8 mg/kg, i.p.). Studies of mice’s hippocampi showed that the response of ampelopsin A was responsible for the restoration of the cholinergic deficits and molecular signal cascades via BDNF/CREB pathways. In conclusion, the central administration of ampelopsin A contributes to increasing neurocognitive and neuroprotective effects on intrinsic neuronal excitability and behaviors, partly through elevated BDNF/CREB-related signaling. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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14 pages, 4017 KiB

Open AccessArticle

Determination of the Antioxidant Activity of Samples of Tea and Commercial Sources of Vitamin C, Using an Enzymatic Biosensor

by Danilo Braga Ribeiro, Gabriela Santos Silva, Djanira Rubim dos Santos, Andressa Rose Castro Costa, Eliane Braga Ribeiro, Mihaela Badea and Gilvanda Silva Nunes

Antioxidants 2021, 10(2), 324; https://doi.org/10.3390/antiox10020324 - 22 Feb 2021

Cited by 10 | Viewed by 3007

Abstract

Antioxidants are synthetic or natural compounds capable of preventing or delaying oxidative damage caused by chemical species that can oxidize cell biomolecules, such as proteins, membranes, and DNA, leading to the development of various pathologies, such as cancer, atherosclerosis, Parkinson, Alzheimer, and other diseases serious. In this study, an amperometric biosensor was used to determine the antioxidant activity of teas and effervescent products based on vitamin C, available on the market. A sensor composed of three electrodes was used. The performance of the following electrochemical mediators was evaluated: meldola blue combined with Reineck salt (MBRS), Prussian blue (PB), and cobalt phthalocyanine (CoPC), as well as the time of polymerization in the enzymatic immobilization process and the agitation process during chronoamperometric measurements. Prussian blue proved to be more efficient as a mediator for the desired purposes. After optimizing the construction stages of the biosensor, as well as the operational parameters, it presented stability for a period of 7 months. The results clearly indicate that the biosensor can be successfully used to detect fraud in products called “antioxidants” or even in drugs containing less ascorbic acid than indicated on the labels. The detection limit was set at 4.93 µmol·L⁻¹. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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25 pages, 2758 KiB

Open AccessArticle

Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults with Subjective Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study

by Jennifer L. Robinson, Julio A. Yanes, Meredith A. Reid, Jerry E. Murphy, Jessica N. Busler, Petey W. Mumford, Kaelin C. Young, Zbigniew J. Pietrzkowski, Boris V. Nemzer, John M. Hunter and Darren T. Beck

Antioxidants 2021, 10(2), 144; https://doi.org/10.3390/antiox10020144 - 20 Jan 2021

Cited by 13 | Viewed by 4663

Abstract

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with polyphenol-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we (1) compared 100 mg of WCCE to a placebo using an acute, randomized, double-blind, within-subject, cross-over design, and we (2) conducted a phytochemical analysis of WCCE. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from the acute administration of WCCE. We hypothesized that WCCE would increase brain-derived neurotrophic factor (BDNF) and glutamate levels while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and accuracy. Participants underwent four neuroimaging scans (pre- and post-WCCE and placebo) to assess neurofunctional/metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy. The results suggest that polyphenol-rich WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision-making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and an increased glutamate/gamma-aminobutyric acid (GABA) ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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22 pages, 4615 KiB

Open AccessArticle

(−)-Epicatechin—An Important Contributor to the Antioxidant Activity of Japanese Knotweed Rhizome Bark Extract as Determined by Antioxidant Activity-Guided Fractionation

by Urška Jug, Katerina Naumoska and Irena Vovk

Antioxidants 2021, 10(1), 133; https://doi.org/10.3390/antiox10010133 - 18 Jan 2021

Cited by 29 | Viewed by 4050

Abstract

The antioxidant activities of Japanese knotweed rhizome bark extracts, prepared with eight different solvents or solvent mixtures (water, methanol, 80% methanol_(aq), acetone, 70% acetone_(aq), ethanol, 70% ethanol_(aq), and 90% ethyl acetate_(aq)), were determined using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay. Low half maximal inhibitory concentration (IC₅₀) values (2.632–3.720 µg mL⁻¹) for all the extracts were in the range of the IC₅₀ value of the known antioxidant ascorbic acid at t₀ (3.115 µg mL⁻¹). Due to the highest extraction yield (~44%), 70% ethanol_(aq) was selected for the preparation of the extract for further investigations. The IC₅₀ value calculated for its antioxidant activity remained stable for at least 14 days, while the IC₅₀ of ascorbic acid increased over time. The stability study showed that the container material was of great importance for the light-protected storage of the ascorbic acid_(aq) solution in a refrigerator. Size exclusion–high-performance liquid chromatography (SEC-HPLC)–UV and reversed phase (RP)-HPLC-UV coupled with multistage mass spectrometry (MSⁿ) were developed for fractionation of the 70% ethanol_(aq) extract and for further compound identification, respectively. In the most potent antioxidant SEC fraction, determined using an on-line post-column SEC-HPLC-DPPH assay, epicatechin, resveratrol malonyl hexoside, and its in-source fragments (resveratrol and resveratrol acetyl hexoside) were tentatively identified by RP-HPLC-MSⁿ. Moreover, epicatechin was additionally confirmed by two orthogonal methods, SEC-HPLC-UV and high-performance thin-layer chromatography (HPTLC) coupled with densitometry. Finally, the latter technique enabled the identification of (−)-epicatechin. (−)-Epicatechin demonstrated potent and stable time-dependent antioxidant activity (IC₅₀ value ~1.5 µg mL⁻¹) for at least 14 days. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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16 pages, 3930 KiB

Open AccessArticle

Natural Food Supplements Reduce Oxidative Stress in Primary Neurons and in the Mouse Brain, Suggesting Applications in the Prevention of Neurodegenerative Diseases

by Miriam Bobadilla, Josune García-Sanmartín and Alfredo Martínez

Antioxidants 2021, 10(1), 46; https://doi.org/10.3390/antiox10010046 - 02 Jan 2021

Cited by 16 | Viewed by 4054

Abstract

Neurodegenerative diseases pose a major health problem for developed countries, and stress has been identified as one of the main risk factors in the development of these disorders. Here, we have examined the protective properties against oxidative stress of several bioactive natural food supplements. We found that MecobalActive^®, Olews^®, and red and white grape seed polyphenol extracts may have a neuroprotective effect in vitro, both in the SH-SY 5Y cell line and in hippocampal neuron cultures, mainly by reducing reactive oxygen species levels and decreasing caspase-3 activity. In vivo, we demonstrated that oral administration of the supplements reduces the expression of genes involved in inflammation and oxidation mechanisms, whereas it increments the expression of genes related to protection against oxidative stress. Furthermore, we found that preventive treatment with these natural extracts increases the activity of antioxidant enzymes and prevents lipid peroxidation in the brain of stressed mice. Thus, our results indicate that some natural bioactive supplements may have important protective properties against oxidative stress processes occurring in the brain. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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Review

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15 pages, 840 KiB

Open AccessReview

Therapeutic Potential of Polyphenols in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

by Valentina Novak, Boris Rogelj and Vera Župunski

Antioxidants 2021, 10(8), 1328; https://doi.org/10.3390/antiox10081328 - 23 Aug 2021

Cited by 23 | Viewed by 4308

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are severe neurodegenerative disorders that belong to a common disease spectrum. The molecular and cellular aetiology of the spectrum is a highly complex encompassing dysfunction in many processes, including mitochondrial dysfunction and oxidative stress. There is a paucity of treatment options aside from therapies with subtle effects on the post diagnostic lifespan and symptom management. This presents great interest and necessity for the discovery and development of new compounds and therapies with beneficial effects on the disease. Polyphenols are secondary metabolites found in plant-based foods and are well known for their antioxidant activity. Recent research suggests that they also have a diverse array of neuroprotective functions that could lead to better treatments for neurodegenerative diseases. We present an overview of the effects of various polyphenols in cell line and animal models of ALS/FTD. Furthermore, possible mechanisms behind actions of the most researched compounds (resveratrol, curcumin and green tea catechins) are discussed. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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23 pages, 1094 KiB

Open AccessReview

Olive Polyphenols: Antioxidant and Anti-Inflammatory Properties

by Monica Bucciantini, Manuela Leri, Pamela Nardiello, Fiorella Casamenti and Massimo Stefani

Antioxidants 2021, 10(7), 1044; https://doi.org/10.3390/antiox10071044 - 29 Jun 2021

Cited by 92 | Viewed by 11049

Abstract

Oxidative stress and inflammation triggered by increased oxidative stress are the cause of many chronic diseases. The lack of anti-inflammatory drugs without side-effects has stimulated the search for new active substances. Plant-derived compounds provide new potential anti-inflammatory and antioxidant molecules. Natural products are structurally optimized by evolution to serve particular biological functions, including the regulation of endogenous defense mechanisms and interaction with other organisms. This property explains their relevance for infectious diseases and cancer. Recently, among the various natural substances, polyphenols from extra virgin olive oil (EVOO), an important element of the Mediterranean diet, have aroused growing interest. Extensive studies have shown the potent therapeutic effects of these bioactive molecules against a series of chronic diseases, such as cardiovascular diseases, diabetes, neurodegenerative disorders and cancer. This review begins from the chemical structure, abundance and bioavailability of the main EVOO polyphenols to highlight the effects and the possible molecular mechanism(s) of action of these compounds against inflammation and oxidation, in vitro and in vivo. In addition, the mechanisms of inhibition of molecular signaling pathways activated by oxidative stress by EVOO polyphenols are discussed, together with their possible roles in inflammation-mediated chronic disorders, also taking into account meta-analysis of population studies and clinical trials. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)

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