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Special Issue "Natural Products and Neuroprotection"

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 May 2019).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Cristina Angeloni
Website
Guest Editor
Prof. Dr. David Vauzour
Website SciProfiles
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
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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. Nowadays, 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 signaling 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

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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 (18 papers)

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Editorial

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Open AccessEditorial
Natural Products and Neuroprotection
Int. J. Mol. Sci. 2019, 20(22), 5570; https://doi.org/10.3390/ijms20225570 - 07 Nov 2019
Cited by 4
Abstract
Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide, and their incidence is dramatically growing together with increased lifespan [...] Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available

Research

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Open AccessArticle
Elucidation of the Molecular Mechanism Underlying Lippia citriodora(Lim.)-Induced Relaxation and Anti-Depression
Int. J. Mol. Sci. 2019, 20(14), 3556; https://doi.org/10.3390/ijms20143556 - 20 Jul 2019
Cited by 2
Abstract
Lippia citriodora ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and [...] Read more.
Lippia citriodora ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and Vs in vivo and in vitro, on human neurotypic SH-SY5Y cells.TST was conducted on mice treated orally with VEE (25, 50 and 100 mg/Kg), Vs (2.5 and 5 mg/Kg), Bupropion (20 mg/Kg) and Milli-Q water. Higher dose of VEE-treated mice showed an increase of immobility time compared to control groups, indicating an induction of relaxation. This effect was found to be induced by regulation of genes playing key roles in calcium homeostasis (calcium channels), cyclic AMP (cAMP) production and energy metabolism. On the other hand, low doses of VEE and Vs showed an antidepressant-like effect and was confirmed by serotonin, noradrenalin, dopamine and BDNF expressions. Finally, VEE and Vsenhancedcell viability, mitochondrial activity and calcium uptake in vitro confirming in vivo findings. Our results showed induction of relaxation and antidepressant-like effects depending on the administered dose of VEE and Vs, through modulation of cAMP and calcium. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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Open AccessArticle
Flavonoids from Chionanthus retusus (Oleaceae) Flowers and Their Protective Effects against Glutamate-Induced Cell Toxicity in HT22 Cells
Int. J. Mol. Sci. 2019, 20(14), 3517; https://doi.org/10.3390/ijms20143517 - 18 Jul 2019
Cited by 4
Abstract
The dried flowers of Chionanthus retusus were extracted with 80% MeOH, and the concentrate was divided into EtOAc, n-BuOH, and H2O fractions. Repeated SiO2, octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatography of the EtOAc fraction led [...] Read more.
The dried flowers of Chionanthus retusus were extracted with 80% MeOH, and the concentrate was divided into EtOAc, n-BuOH, and H2O fractions. Repeated SiO2, octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatography of the EtOAc fraction led to the isolation of four flavonols (14), three flavones (57), four flavanonols (811), and one flavanone (12), which were identified based on extensive analysis of various spectroscopic data. Flavonoids 46 and 811 were isolated from the flowers of C. retusus for the first time in this study. Flavonoids 1, 2, 5, 6, 8, and 1012 significantly inhibited NO production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) and glutamate-induced cell toxicity and effectively increased HO-1 protein expression in mouse hippocampal HT22 cells. Flavonoids with significant neuroprotective activity were also found to recover oxidative-stress-induced cell damage by increasing HO-1 protein expression. This article demonstrates that flavonoids from C. retusus flowers have significant potential as therapeutic materials in inflammation and neurodisease. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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Open AccessArticle
Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species
Int. J. Mol. Sci. 2019, 20(14), 3409; https://doi.org/10.3390/ijms20143409 - 11 Jul 2019
Cited by 5
Abstract
Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic reagent that specifically [...] Read more.
Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic reagent that specifically protects neurotoxin-induced reduction of mitochondrial respiration and inhibits reactive oxygen species (ROS) generation. Further, we explored the mechanism and potency of AUR in protecting dopaminergic neurons. Treatment with AUR significantly increased the viability of substantia nigra (SN)-derived SN4741 embryonic dopaminergic neuronal cells and reduced rotenone-induced mitochondrial ROS production. By inducing antioxidant enzymes AUR treatment also increased oxygen consumption rate. These results indicate that AUR exerts a protective effect against rotenone-induced mitochondrial oxidative damage. We further assessed AUR effects in vivo, investigating tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of MPTP-induced PD model mice and behavioral changes after injection of AUR. AUR treatment improved movement, consistent with the observed increase in the number of dopaminergic neurons in the substantia nigra. These results demonstrate that AUR targets dual pathogenic mechanisms, enhancing mitochondrial respiration and attenuating ROS production, suggesting that the preventative potential of this natural compound could lead to improvement in PD-related neurobiological changes. Full article
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Open AccessArticle
Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer’s Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus
Int. J. Mol. Sci. 2019, 20(8), 1871; https://doi.org/10.3390/ijms20081871 - 16 Apr 2019
Cited by 9
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat’s hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture. Full article
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Open AccessArticle
Neuroprotective Effects of Thymol, a Dietary Monoterpene Against Dopaminergic Neurodegeneration in Rotenone-Induced Rat Model of Parkinson’s Disease
Int. J. Mol. Sci. 2019, 20(7), 1538; https://doi.org/10.3390/ijms20071538 - 27 Mar 2019
Cited by 12
Abstract
Parkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was [...] Read more.
Parkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes. Full article
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Review

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Open AccessReview
Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson’s Disease Models
Int. J. Mol. Sci. 2019, 20(20), 5208; https://doi.org/10.3390/ijms20205208 - 21 Oct 2019
Cited by 6
Abstract
Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of [...] Read more.
Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD. Full article
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Open AccessReview
Natural Products in Neurodegenerative Diseases: A Great Promise but an Ethical Challenge
Int. J. Mol. Sci. 2019, 20(20), 5170; https://doi.org/10.3390/ijms20205170 - 18 Oct 2019
Cited by 7
Abstract
Neurodegenerative diseases (NDs) represent one of the most important public health problems and concerns, as they are a growing cause of mortality and morbidity worldwide, particularly in the elderly. Despite remarkable breakthroughs in our understanding of NDs, there has been little success in [...] Read more.
Neurodegenerative diseases (NDs) represent one of the most important public health problems and concerns, as they are a growing cause of mortality and morbidity worldwide, particularly in the elderly. Despite remarkable breakthroughs in our understanding of NDs, there has been little success in developing effective therapies. The use of natural products may offer great potential opportunities in the prevention and therapy of NDs; however, many clinical concerns have arisen regarding their use, mainly focusing on the lack of scientific support or evidence for their efficacy and patient safety. These clinical uncertainties raise critical questions from a bioethical and legal point of view, as considerations relating to patient decisional autonomy, patient safety, and beneficial or non-beneficial care may need to be addressed. This paper does not intend to advocate for or against the use of natural products, but to analyze the ethical framework of their use, with particular attention paid to the principles of biomedical ethics. In conclusion, the notable message that emerges is that natural products may represent a great promise for the treatment of many NDs, even if many unknown issues regarding the efficacy and safety of many natural products still remain. Full article
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Open AccessReview
Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases
Int. J. Mol. Sci. 2019, 20(19), 4666; https://doi.org/10.3390/ijms20194666 - 20 Sep 2019
Cited by 2
Abstract
Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage. Protein homeostasis or proteostasis [...] Read more.
Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage. Protein homeostasis or proteostasis comprises a complex interconnected network that regulates different steps of the protein quality control, from synthesis and folding, to degradation. Due to the primary role of proteins in cellular function, the integrity of this network is critical to assure functionality and health across lifespan. Proteostasis failure has been reported in the context of aging and neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Therefore, targeting the proteostasis elements emerges as a promising neuroprotective therapeutic approach to prevent or ameliorate the progression of these disorders. A variety of natural products are known to be neuroprotective by protein homeostasis interaction. In this review, we will focus on the current knowledge regarding the use of natural products as modulators of different components of the proteostasis machinery within the framework of age-associated neurodegenerative diseases. Full article
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Open AccessReview
Ascaroside Pheromones: Chemical Biology and Pleiotropic Neuronal Functions
Int. J. Mol. Sci. 2019, 20(16), 3898; https://doi.org/10.3390/ijms20163898 - 09 Aug 2019
Cited by 5
Abstract
Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this [...] Read more.
Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal β-oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid β-oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of pheromics (pheromone omics) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones. Full article
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Open AccessReview
Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites
Int. J. Mol. Sci. 2019, 20(15), 3630; https://doi.org/10.3390/ijms20153630 - 25 Jul 2019
Cited by 21
Abstract
Over the last three decades, green tea has been studied for its beneficial effects, including anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory, and neuroprotective effects. At present, a number of studies that have employed animal, human and cell cultures support the potential neuroprotective effects of green [...] Read more.
Over the last three decades, green tea has been studied for its beneficial effects, including anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory, and neuroprotective effects. At present, a number of studies that have employed animal, human and cell cultures support the potential neuroprotective effects of green tea catechins against neurological disorders. However, the concentration of (−)-epigallocatechin gallate (EGCG) in systemic circulation is very low and EGCG disappears within several hours. EGCG undergoes microbial degradation in the small intestine and later in the large intestine, resulting in the formation of various microbial ring-fission metabolites which are detectable in the plasma and urine as free and conjugated forms. Recently, in vitro experiments suggested that EGCG and its metabolites could reach the brain parenchyma through the blood–brain barrier and induce neuritogenesis. These results suggest that metabolites of EGCG may play an important role, alongside the beneficial activities of EGCG, in reducing neurodegenerative diseases. In this review, we discuss the function of EGCG and its microbial ring-fission metabolites in the brain in suppressing brain dysfunction. Other possible actions of EGCG metabolites will also be discussed. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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Open AccessReview
Anti-Inflammatory Activities of Marine Algae in Neurodegenerative Diseases
Int. J. Mol. Sci. 2019, 20(12), 3061; https://doi.org/10.3390/ijms20123061 - 22 Jun 2019
Cited by 12
Abstract
Neuroinflammation is one of the main contributors to the onset and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Microglial and astrocyte activation is a brain defense mechanism to counteract harmful pathogens and damaged tissues, while their prolonged activation induces neuroinflammation [...] Read more.
Neuroinflammation is one of the main contributors to the onset and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Microglial and astrocyte activation is a brain defense mechanism to counteract harmful pathogens and damaged tissues, while their prolonged activation induces neuroinflammation that can trigger or exacerbate neurodegeneration. Unfortunately, to date there are no pharmacological therapies able to slow down or stop the progression of neurodegeneration. For this reason, research is turning to the identification of natural compounds with protective action against these diseases. Considering the important role of neuroinflammation in the onset and development of neurodegenerative pathologies, natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Marine organisms represent a huge source of natural compounds, and among them, algae are appreciated sources of important bioactive components such as antioxidants, proteins, vitamins, minerals, soluble dietary fibers, polyunsaturated fatty acids, polysaccharides, sterols, carotenoids, tocopherols, terpenes, phycobilins, phycocolloids, and phycocyanins. Recently, numerous anti-inflammatory compounds have been isolated from marine algae with potential protective efficacy against neuroinflammation. This review highlights the key inflammatory processes involved in neurodegeneration and the potential of specific compounds from marine algae to counteract neuroinflammation in the CNS. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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Open AccessReview
The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases
Int. J. Mol. Sci. 2019, 20(12), 3056; https://doi.org/10.3390/ijms20123056 - 22 Jun 2019
Cited by 18
Abstract
Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of [...] Read more.
Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of the underlying cause of the disorder, age is the strongest risk factor for developing these maladies, suggesting that changes that occur in the aging brain put it at increased risk for neurodegenerative disease development. Moreover, since there are a number of different changes that occur in the aging brain, it is unlikely that targeting a single change is going to be effective for disease treatment. Thus, compounds that have multiple biological activities that can impact the various age-associated changes in the brain that contribute to neurodegenerative disease development and progression are needed. The plant-derived flavonoids have a wide range of activities that could make them particularly effective for blocking the age-associated toxicity pathways associated with neurodegenerative diseases. In this review, the evidence for beneficial effects of multiple flavonoids in models of AD, PD, HD, and ALS is presented and common mechanisms of action are identified. Overall, the preclinical data strongly support further investigation of specific flavonoids for the treatment of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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Open AccessReview
Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus
Int. J. Mol. Sci. 2019, 20(10), 2533; https://doi.org/10.3390/ijms20102533 - 23 May 2019
Cited by 7
Abstract
Diabetes mellitus is a chronic metabolic disease with a high prevalence in the Western population. It is characterized by pancreas failure to produce insulin, which involves high blood glucose levels. The two main forms of diabetes are type 1 and type 2 diabetes, [...] Read more.
Diabetes mellitus is a chronic metabolic disease with a high prevalence in the Western population. It is characterized by pancreas failure to produce insulin, which involves high blood glucose levels. The two main forms of diabetes are type 1 and type 2 diabetes, which correspond with >85% of the cases. Diabetes shows several associated alterations including vascular dysfunction, neuropathies as well as central complications. Brain alterations in diabetes are widely studied; however, the mechanisms implicated have not been completely elucidated. Diabetic brain shows a wide profile of micro and macrostructural changes, such as neurovascular deterioration or neuroinflammation leading to neurodegeneration and progressive cognition dysfunction. Natural compounds (single isolated compounds and/or natural extracts) have been widely assessed in metabolic disorders and many of them have also shown antioxidant, antiinflamatory and neuroprotective properties at central level. This work reviews natural compounds with brain neuroprotective activities, taking into account several therapeutic targets: Inflammation and oxidative stress, vascular damage, neuronal loss or cognitive impairment. Altogether, a wide range of natural extracts and compounds contribute to limit neurodegeneration and cognitive dysfunction under diabetic state. Therefore, they could broaden therapeutic alternatives to reduce or slow down complications associated with diabetes at central level. Full article
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Open AccessReview
Curcumin and Heme Oxygenase: Neuroprotection and Beyond
Int. J. Mol. Sci. 2019, 20(10), 2419; https://doi.org/10.3390/ijms20102419 - 16 May 2019
Cited by 6
Abstract
Curcumin is a natural polyphenol component of Curcuma longa Linn, which is currently considered one of the most effective nutritional antioxidants for counteracting free radical-related diseases. Several experimental data have highlighted the pleiotropic neuroprotective effects of curcumin, due to its activity in [...] Read more.
Curcumin is a natural polyphenol component of Curcuma longa Linn, which is currently considered one of the most effective nutritional antioxidants for counteracting free radical-related diseases. Several experimental data have highlighted the pleiotropic neuroprotective effects of curcumin, due to its activity in multiple antioxidant and anti-inflammatory pathways involved in neurodegeneration. Although its poor systemic bioavailability after oral administration and low plasma concentrations represent restrictive factors for curcumin therapeutic efficacy, innovative delivery formulations have been developed in order to overwhelm these limitations. This review provides a summary of the main findings involving the heme oxygenase/biliverdin reductase system as a valid target in mediating the potential neuroprotective properties of curcumin. Furthermore, pharmacokinetic properties and concerns about curcumin’s safety profile have been addressed. Full article
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Open AccessReview
Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies
Int. J. Mol. Sci. 2019, 20(9), 2313; https://doi.org/10.3390/ijms20092313 - 10 May 2019
Cited by 28
Abstract
Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase [...] Read more.
Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benefits for this neurological disease, focusing on studies that present clinical trials. Full article
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Open AccessReview
Considerations for the Use of Polyphenols as Therapies in Neurodegenerative Diseases
Int. J. Mol. Sci. 2019, 20(8), 1883; https://doi.org/10.3390/ijms20081883 - 16 Apr 2019
Cited by 24
Abstract
Over the last two decades, the increase in the incidence of neurodegenerative diseases due to the increasingly ageing population has resulted in a major social and economic burden. At present, a large body of literature supports the potential use of functional nutrients, which [...] Read more.
Over the last two decades, the increase in the incidence of neurodegenerative diseases due to the increasingly ageing population has resulted in a major social and economic burden. At present, a large body of literature supports the potential use of functional nutrients, which exhibit potential neuroprotective properties to mitigate these diseases. Among the most studied dietary molecules, polyphenols stand out because of their multiple and often overlapping reported modes of action. However, ambiguity still exists as to the significance of their influence on human health. This review discusses the characteristics and functions of polyphenols that shape their potential therapeutic actions in neurodegenerative diseases while the less-explored gaps in knowledge of these nutrients will also be highlighted. Full article
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Open AccessReview
Effectiveness of Vitamin D Supplementation in the Management of Multiple Sclerosis: A Systematic Review
Int. J. Mol. Sci. 2019, 20(6), 1301; https://doi.org/10.3390/ijms20061301 - 14 Mar 2019
Cited by 11
Abstract
Objective: to examine the extent of effect vitamin D in Multiple Sclerosis (MS) on pathology and symptoms. Methods: A literature search was performed in November 2018 (CRD42018103615). Eligibility criteria: randomised control trials in English from 2012 to 2018; a clinical diagnosis of MS; [...] Read more.
Objective: to examine the extent of effect vitamin D in Multiple Sclerosis (MS) on pathology and symptoms. Methods: A literature search was performed in November 2018 (CRD42018103615). Eligibility criteria: randomised control trials in English from 2012 to 2018; a clinical diagnosis of MS; interventions containing vitamin D supplementation (vitamin D3 or calcitriol) in disease activity compared to a control/placebo; improvement in: serum 25(OH)D, relapse rates, disability status by Expanded Disability Status Scale (EDSS) scores, cytokine profile, quality of life, mobility, T2 lesion load and new T2 or T1 Gd enhancing lesions, safety and adverse effects. Risk of bias was evaluated. Results: Ten studies were selected. The study size ranged from 40 to 94 people. All studies evaluated the use of vitamin D supplementation (ranging from 10 to 98,000 IU), comparing to a placebo or low dose vitamin D. The duration of the intervention ranged from 12 to 96 weeks. One trial found a significant effect on EDSS score, three demonstrated a significant change in serum cytokines level, one found benefits to current enhancing lesions and three studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. Disease measures improved to a greater extent overall in those with lower baseline serum 25(OH)D levels. Conclusions: As shown in 3 out of 10 studies, improvement in disease measures may be more apparent in those with lower baseline vitamin D levels. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection) Printed Edition available
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