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Natural Products and Neuroprotection 2.0
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Natural Products and Neuroprotection 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 68773

Special Issue Editors

Dr. Cristina Angeloni

E-Mail Website
Guest Editor
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
Interests: nutritional biochemistry; neurodegenerative diseases; oxidative stress; inflammation; nutraceuticals; ageing
Special Issues, Collections and Topics in MDPI journals
Dr. David Vauzour

E-Mail Website
Guest Editor
Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich NR4 7UQ, UK
Interests: neurodegenerative disorders; phytochemicals; neuroinflammation; memory; learning and neuro-cognitive performances; signalling pathways; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide, and their incidence is dramatically growing together with increased lifespan. These diseases are a heterogenous group of chronic, progressive disorders characterized by the gradual loss of neurons in the central nervous system, which leads to deficits in specific brain functions. The most common neurodegenerative diseases are Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington’s disease. These multifactorial debilitating disorders share common molecular and cellular characteristics, such as oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and inflammation. Presently, there are no therapeutic approaches to cure or even halt the progression of these disorders. In this context, natural products, because of their broad spectrum of pharmacological and biological activities, are considered promising alternatives for the treatment of neurodegeneration. Natural compounds have been recognized to possess different biological activities, including antioxidant, anti-inflammatory, and antiapoptotic effects. Moreover, natural compounds have been recently shown to counteract protein misfolding and to modulate autophagy and proteasome activity.

In this Special Issue, we invite investigators to contribute original research articles, as well as review articles regarding the biological effect of natural products in preventing/counteracting neurodegeneration.

Topics include but are not limited to the following:

  • Clinical or preclinical studies investigating natural products in the treatment of neurodegenerative diseases;
  • The role of natural products in counteracting oxidative stress in neurodegeneration;
  • The role of natural products in counteracting inflammation in neurodegeneration;
  • The use of natural products in modulating autophagy and proteasome activity to counteract abnormal protein aggregation in neurodegeneration;
  • The role of natural products in modulating signalling pathways involved in neurodegeneration;
  • The use of natural products as lead compounds in drug discovery for the treatment of neurodegenerative diseases.

Prof. Dr. Cristina Angeloni
Prof. Dr. David Vauzour
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Oxidative stress
  • Inflammation
  • Protein misfolding
  • Natural compounds
  • Nutraceuticals
  • Phytochemicals
  • Neurodegeneration
  • Alzheimer’s disease
  • Parkinson’s disease
  • Amyotrophic lateral sclerosis
  • Multiple sclerosis
  • Huntington’s disease

Published Papers (10 papers)

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Research

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15 pages, 1831 KiB  
Article
Theanine, Antistress Amino Acid in Tea Leaves, Causes Hippocampal Metabolic Changes and Antidepressant Effects in Stress-Loaded Mice
by Keiko Unno, Yoshio Muguruma, Koichi Inoue, Tomokazu Konishi, Kyoko Taguchi, Sanae Hasegawa-Ishii, Atsuyoshi Shimada and Yoriyuki Nakamura
Int. J. Mol. Sci. 2021, 22(1), 193; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010193 - 28 Dec 2020
Cited by 9 | Viewed by 2628
Abstract
By comprehensively measuring changes in metabolites in the hippocampus of stress-loaded mice, we investigated the reasons for stress vulnerability and the effect of theanine, i.e., an abundant amino acid in tea leaves, on the metabolism. Stress sensitivity was higher in senescence-accelerated mouse prone [...] Read more.
By comprehensively measuring changes in metabolites in the hippocampus of stress-loaded mice, we investigated the reasons for stress vulnerability and the effect of theanine, i.e., an abundant amino acid in tea leaves, on the metabolism. Stress sensitivity was higher in senescence-accelerated mouse prone 10 (SAMP10) mice than in normal ddY mice when these mice were loaded with stress on the basis of territorial consciousness in males. Group housing was used as the low-stress condition reference. Among the statistically altered metabolites, depression-related kynurenine and excitability-related histamine were significantly higher in SAMP10 mice than in ddY mice. In contrast, carnosine, which has antidepressant-like activity, and ornithine, which has antistress effects, were significantly lower in SAMP10 mice than in ddY mice. The ingestion of theanine, an excellent antistress amino acid, modulated the levels of kynurenine, histamine, and carnosine only in the stress-loaded SAMP10 mice and not in the group-housing mice. Depression-like behavior was suppressed in mice that had ingested theanine only under stress loading. Taken together, changes in these metabolites, such as kynurenine, histamine, carnosine, and ornithine, were suggested to be associated with the stress vulnerability and depression-like behavior of stressed SAMP10 mice. It was also shown that theanine action appears in the metabolism of mice only under stress loading. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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27 pages, 2922 KiB  
Article
In Silico Studies on Triterpenoid Saponins Permeation through the Blood–Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration
by Katarzyna Stępnik and Wirginia Kukula-Koch
Int. J. Mol. Sci. 2020, 21(7), 2534; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072534 - 05 Apr 2020
Cited by 15 | Viewed by 3000
Abstract
As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this study was to [...] Read more.
As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this study was to evaluate the ability to cross the BBB of triterpenoid saponins occurring in Astragalus mongholicus roots. The research was carried out using in silico methods combined with postmortem studies on the brain tissues of mice treated with isolated astragaloside IV (AIV). Firstly, to estimate the ability to cross the BBB by the tested saponins, new quantitative structure–activity relationship (QSAR) models were established. The reliability and predictability of the model based on the values of the blood–brain barrier penetration descriptor (logBB), the difference between the n-octanol/water and cyclohexane/water logP (ΔlogP), the logarithm of n-octanol/water partition coefficient (logPow), and the excess molar refraction (E) were both confirmed using the applicability domain (AD). The critical leverage value h* was found to be 0.128. The relationships between the standardized residuals and the leverages were investigated here. The application of an in vitro acetylcholinesterase-inhibition test showed that AIV can be recognized as the strongest inhibitor among the tested compounds. Therefore, it was isolated for the postmortem studies on brain tissues and blood using semi-preparative HPLC with the mobile phase composed of water, methanol, and ethyl acetate (1.7:2.1:16.2 v/v/v). The results of the postmortem studies on the brain tissues show a regular dependence of the final concentration of AIV in the analyzed brain samples of animals treated with 12.5 and 25 mg/kg b.w. of AIV (0.00012299 and 0.0002306 mg, respectively, per one brain). Moreover, the AIV logBB value was experimentally determined and found to be equal to 0.49 ± 0.03. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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Review

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37 pages, 1048 KiB  
Review
Nutraceuticals in the Prevention of Neonatal Hypoxia–Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions
by Marta Reyes-Corral, Noelia Sola-Idígora, Rocío de la Puerta, Joan Montaner and Patricia Ybot-González
Int. J. Mol. Sci. 2021, 22(5), 2524; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052524 - 03 Mar 2021
Cited by 10 | Viewed by 3735
Abstract
Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of [...] Read more.
Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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25 pages, 2846 KiB  
Review
Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid
by Fanni Tóth, Edina Katalin Cseh and László Vécsei
Int. J. Mol. Sci. 2021, 22(1), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010403 - 02 Jan 2021
Cited by 38 | Viewed by 5608
Abstract
The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression [...] Read more.
The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression of the disease and prevent neuronal death. Some natural products and molecules are very promising neuroprotective agents because of their structural diversity and wide variety of biological activities. In addition to their neuroprotective effect, they are known for their antioxidant, anti-inflammatory and antiapoptotic effects and often serve as a starting point for drug discovery. In this review, the following natural molecules are discussed: firstly, kynurenic acid, the main neuroprotective agent formed via the kynurenine pathway of tryptophan metabolism, as it is known mainly for its role in glutamate excitotoxicity, secondly, the dietary supplement pantethine, that is many sided, well tolerated and safe, and the third molecule, α-lipoic acid is a universal antioxidant. As a conclusion, because of their beneficial properties, these molecules are potential candidates for neuroprotective therapies suitable in managing neurodegenerative diseases. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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64 pages, 1479 KiB  
Review
Neuroprotective Effects of Coffee Bioactive Compounds: A Review
by Katarzyna Socała, Aleksandra Szopa, Anna Serefko, Ewa Poleszak and Piotr Wlaź
Int. J. Mol. Sci. 2021, 22(1), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010107 - 24 Dec 2020
Cited by 99 | Viewed by 17667
Abstract
Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a [...] Read more.
Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a number of bioactive compounds such as polyphenols, especially chlorogenic acids (in green beans) and caffeic acid (in roasted coffee beans), alkaloids (caffeine and trigonelline), and the diterpenes (cafestol and kahweol). Extensive research shows that coffee consumption appears to have beneficial effects on human health. Regular coffee intake may protect from many chronic disorders, including cardiovascular disease, type 2 diabetes, obesity, and some types of cancer. Importantly, coffee consumption seems to be also correlated with a decreased risk of developing some neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and dementia. Regular coffee intake may also reduce the risk of stroke. The mechanism underlying these effects is, however, still poorly understood. This review summarizes the current knowledge on the neuroprotective potential of the main bioactive coffee components, i.e., caffeine, chlorogenic acid, caffeic acid, trigonelline, kahweol, and cafestol. Data from both in vitro and in vivo preclinical experiments, including their potential therapeutic applications, are reviewed and discussed. Epidemiological studies and clinical reports on this matter are also described. Moreover, potential molecular mechanism(s) by which coffee bioactive components may provide neuroprotection are reviewed. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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11 pages, 748 KiB  
Review
Antitumor Activity of Curcumin in Glioblastoma
by Blake C. Walker and Sandeep Mittal
Int. J. Mol. Sci. 2020, 21(24), 9435; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249435 - 11 Dec 2020
Cited by 36 | Viewed by 4266
Abstract
Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® [...] Read more.
Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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31 pages, 1619 KiB  
Review
The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders
by Joana F. Henriques, Diana Serra, Teresa C. P. Dinis and Leonor M. Almeida
Int. J. Mol. Sci. 2020, 21(22), 8653; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228653 - 17 Nov 2020
Cited by 48 | Viewed by 5661
Abstract
Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a [...] Read more.
Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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26 pages, 1107 KiB  
Review
Efficacy of Sulforaphane in Neurodegenerative Diseases
by Giovanni Schepici, Placido Bramanti and Emanuela Mazzon
Int. J. Mol. Sci. 2020, 21(22), 8637; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228637 - 16 Nov 2020
Cited by 78 | Viewed by 10815
Abstract
Sulforaphane (SFN) is a phytocompound belonging to the isothiocyanate family. Although it was also found in seeds and mature plants, SFN is mainly present in sprouts of many cruciferous vegetables, including cabbage, broccoli, cauliflower, and Brussels sprouts. SFN is produced by the conversion [...] Read more.
Sulforaphane (SFN) is a phytocompound belonging to the isothiocyanate family. Although it was also found in seeds and mature plants, SFN is mainly present in sprouts of many cruciferous vegetables, including cabbage, broccoli, cauliflower, and Brussels sprouts. SFN is produced by the conversion of glucoraphanin through the enzyme myrosinase, which leads to the formation of this isothiocyanate. SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties, and for this reason, it aroused the interest of researchers. The aim of this review is to summarize the experimental studies present on Pubmed that report the efficacy of SFN in the treatment of neurodegenerative disease, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Therefore, thanks to its beneficial effects, SFN could be useful as a supplement to counteracting neurodegenerative diseases. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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23 pages, 1229 KiB  
Review
Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles
by Ha Thi Thu Do and Jungsook Cho
Int. J. Mol. Sci. 2020, 21(17), 6211; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176211 - 27 Aug 2020
Cited by 35 | Viewed by 7429
Abstract
Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (Garcinia mangostana L.,) pericarp (MP) and its xanthones may provide therapeutic advantages for these disorders. In this review, we [...] Read more.
Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (Garcinia mangostana L.,) pericarp (MP) and its xanthones may provide therapeutic advantages for these disorders. In this review, we discuss potential therapeutic value of MP-derived agents in AD, PD, and depression with their pharmacokinetic and safety profiles. MP-derived agents have shown multifunctional effects including neuroprotective, antioxidant, and anti-neuroinflammatory actions. In addition, they target specific disease pathologies, such as amyloid beta production and deposition as well as cholinergic dysfunction in AD; α-synuclein aggregation in PD; and modulation of monoamine disturbance in depression. Particularly, the xanthone derivatives, including α-mangostin and γ-mangostin, exhibit potent pharmacological actions. However, low oral bioavailability and poor brain penetration may limit their therapeutic applications. These challenges can be overcome in part by administering as a form of MP extract (MPE) or using specific carrier systems. MPE and α-mangostin are generally safe and well-tolerated in animals. Furthermore, mangosteen-based products are safe for humans. Therefore, MPE and its bioactive xanthones are promising candidates for the treatment of AD, PD, and depression. Further studies including clinical trials are essential to decipher their efficacy, and pharmacokinetic and safety profiles in these disorders. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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13 pages, 2433 KiB  
Review
Quercetin in Animal Models of Alzheimer’s Disease: A Systematic Review of Preclinical Studies
by Xiao-Wen Zhang, Jia-Yue Chen, Defang Ouyang and Jia-Hong Lu
Int. J. Mol. Sci. 2020, 21(2), 493; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020493 - 13 Jan 2020
Cited by 64 | Viewed by 6391
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid [...] Read more.
Alzheimer’s disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid contained in a wide range of plant species, is repeatedly reported to exert neuroprotective effects in experimental animal AD models. However, a systematic analysis of methodological rigor and the comparison between different studies is still lacking. A systematic review uses a methodical approach to minimize the bias in each independent study, providing a less biased, comprehensive understanding of research findings and an objective judgement of the strength of evidence and the reliability of conclusions. In this review, we identified 14 studies describing the therapeutic efficacy of quercetin on animal AD models by electronic and manual retrieval. Some of the results of the studies included were meta-analyzed by forest plot, and the methodological quality of each preclinical trial was assessed with SYRCLE’s risk of bias tool. Our results demonstrated the consistent neuroprotective effects of quercetin on different AD models, and the pharmacological mechanisms of quercetin on AD models are summarized. This information eliminated the bias of each individual study, providing guidance for future tests and supporting evidence for further implementation of quercetin into clinical trials. However, the limitations of some studies, such as the absence of sample size calculations and low method quality, should also be noted. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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