Editorial

5 pages, 665 KiB

Open AccessEditorial

Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration

by Maria Antonietta Panaro and Chiara Porro

Nutrients 2022, 14(11), 2216; https://doi.org/10.3390/nu14112216 - 26 May 2022

Cited by 3 | Viewed by 1618

Figure 1 summarizes the neuroprotective effects played by bioactive compounds examined in this Special Issue [...] Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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Research

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13 pages, 3048 KiB

Open AccessArticle

Erinacine A-Enriched Hericium erinaceus Mycelium Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice

by Li-Ya Lee, Wayne Chou, Wan-Ping Chen, Ming-Fu Wang, Ying-Ju Chen, Chin-Chu Chen and Kwong-Chung Tung

Nutrients 2021, 13(10), 3659; https://doi.org/10.3390/nu13103659 - 19 Oct 2021

Cited by 12 | Viewed by 3485

Abstract

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve [...] Read more.

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve cognitive disability in Alzheimer’s disease model APP/PS1 mice. However, its effects on brain aging have not yet been touched upon. Here, we used senescence accelerated mouse prone 8 (SAMP8) mice as a model to elucidate the mechanism by which EAHEM delays the aging of the brain. Three-month-old SAMP8 mice were divided into three EAHEM dosage groups, administered at 108, 215 and 431 mg/kg/BW/day, respectively. During the 12th week of EAHEM feeding, learning and memory of the mice were evaluated by single-trial passive avoidance and active avoidance test. After sacrifice, the amyloid plaques, induced nitric oxidase synthase (iNOS) activity, thiobarbituric acid-reactive substances (TBARS) and 8-OHdG levels were analyzed. We found that the lowest dose of 108 mg/kg/BW EAHEM was sufficient to significantly improve learning and memory in the passive and active avoidance tests. In all three EAHEM dose groups, iNOS, TBARS and 8-OHdG levels all decreased significantly and showed a dose-dependent response. The results indicate that EAHEM improved learning and memory and delayed degenerative aging in mice brains. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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35 pages, 10934 KiB

Open AccessArticle

Lactoferrin Protects against Methamphetamine Toxicity by Modulating Autophagy and Mitochondrial Status

by Larisa Ryskalin, Francesca Biagioni, Carla L. Busceti, Maico Polzella, Paola Lenzi, Alessandro Frati, Michela Ferrucci and Francesco Fornai

Nutrients 2021, 13(10), 3356; https://doi.org/10.3390/nu13103356 - 25 Sep 2021

Cited by 5 | Viewed by 3152

Abstract

Lactoferrin (LF) was used at first as a vehicle to deliver non-soluble active compounds to the body, including the central nervous system (CNS). Nonetheless, it soon became evident that, apart from acting as a vehicle, LF itself owns active effects in the CNS. [...] Read more.

Lactoferrin (LF) was used at first as a vehicle to deliver non-soluble active compounds to the body, including the central nervous system (CNS). Nonetheless, it soon became evident that, apart from acting as a vehicle, LF itself owns active effects in the CNS. In the present study, the effects of LF are assessed both in baseline conditions, as well as to counteract methamphetamine (METH)-induced neurodegeneration by assessing cell viability, cell phenotype, mitochondrial status, and specific autophagy steps. In detail, cell integrity in baseline conditions and following METH administration was carried out by using H&E staining, Trypan blue, Fluoro Jade B, and WST-1. Western blot and immuno-fluorescence were used to assess the expression of the neurofilament marker βIII-tubulin. Mitochondria were stained using Mito Tracker Red and Green and were further detailed and quantified by using transmission electron microscopy. Autophagy markers were analyzed through immuno-fluorescence and electron microscopy. LF counteracts METH-induced degeneration. In detail, LF significantly attenuates the amount of cell loss and mitochondrial alterations produced by METH; and mitigates the dissipation of autophagy-related proteins from the autophagy compartment, which is massively induced by METH. These findings indicate a protective role of LF in the molecular mechanisms of neurodegeneration. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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17 pages, 4503 KiB

Open AccessArticle

Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness

by Vanessa Kraft, Katja Schmitz, Annett Wilken-Schmitz, Gerd Geisslinger, Marco Sisignano and Irmgard Tegeder

Nutrients 2021, 13(9), 2953; https://doi.org/10.3390/nu13092953 - 25 Aug 2021

Cited by 2 | Viewed by 2856

Abstract

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as [...] Read more.

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer’s disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice. Therefore, we here assessed the effects of continuous trehalose administration via drinking water using the mouse Spared Nerve Injury model of neuropathic pain. Trehalose had no effect on drinking, feeding, voluntary wheel running, motor coordination, locomotion, and open field, elevated plus maze, and Barnes Maze behavior, showing that it was well tolerated. However, trehalose reduced nerve injury-evoked nociceptive mechanical and thermal hypersensitivity as compared to vehicle. Trehalose had no effect on calcium currents in primary somatosensory neurons, pointing to central mechanisms of the antinociceptive effects. In IntelliCages, trehalose-treated mice showed reduced activity, in particular, a low frequency of nosepokes, which was associated with a reduced proportion of correct trials and flat learning curves in place preference learning tasks. Mice failed to switch corner preferences and stuck to spontaneously preferred corners. The behavior in IntelliCages is suggestive of sedative effects as a “side effect” of a continuous protracted trehalose treatment, leading to impairment of learning flexibility. Hence, trehalose diet supplements might reduce chronic pain but likely at the expense of alertness. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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14 pages, 4056 KiB

Open AccessArticle

Teaghrelin Protects SH-SY5Y Cells against MPP⁺-Induced Neurotoxicity through Activation of AMPK/SIRT1/PGC-1α and ERK1/2 Pathways

by Cian-Fen Jhuo, Sheng-Kuo Hsieh, Chun-Jung Chen, Wen-Ying Chen and Jason T.C. Tzen

Nutrients 2020, 12(12), 3665; https://doi.org/10.3390/nu12123665 - 28 Nov 2020

Cited by 14 | Viewed by 3791

Abstract

The prevalence and incidence of Parkinson’s disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic [...] Read more.

The prevalence and incidence of Parkinson’s disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic treatment for combating PD is limited. The ghrelin axis and ghrelin receptor have been implicated in the preservation of dopaminergic neurons and have potential implications in PD treatment. Teaghrelin, a compound originating from Chin-Shin Oolong tea, exhibits ghrelin agonist activity. In this study, the neuroprotective potential of teaghrelin against PD was explored in a cell model in which human neuroblastoma SH-SY5Y cells were treated with the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP⁺). Upon MPP⁺ exposure, SH-SY5Y cells exhibited decreased mitochondrial complex I activity and apoptotic cell death. Teaghrelin activated AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α) and extracellular signal–regulated kinases 1 and 2 (ERK1/2) pathways to antagonize MPP⁺-induced cell death. Herein, we propose that teaghrelin is a potential candidate for the therapeutic treatment of PD. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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8 pages, 1446 KiB

Open AccessArticle

Discovery of Sulforaphane as a Potent BACE1 Inhibitor Based on Kinetics and Computational Studies

by Kumju Youn, Jeong-Hyun Yoon, Nayoung Lee, Gyutae Lim, Jinhyuk Lee, Shengmin Sang, Chi-Tang Ho and Mira Jun

Nutrients 2020, 12(10), 3026; https://doi.org/10.3390/nu12103026 - 02 Oct 2020

Cited by 12 | Viewed by 3356

Abstract

BACE1 is the rate-limiting enzyme involved in the production and deposition of β-amyloid (Aβ). Since neurotoxic Aβ plays a critical role in Alzheimer’s disease (AD) pathogenesis, BACE1 has emerged as a key target for preventing AD. In the present study, the potential of [...] Read more.

BACE1 is the rate-limiting enzyme involved in the production and deposition of β-amyloid (Aβ). Since neurotoxic Aβ plays a critical role in Alzheimer’s disease (AD) pathogenesis, BACE1 has emerged as a key target for preventing AD. In the present study, the potential of sulforaphane, an isothiocyanate found in cruciferous vegetables, as a BACE1 inhibitor has been investigated. Sulforaphane exhibited six times more potent activity against BACE1 compared to well-known positive controls including resveratrol and quercetin. Sulforaphane presented selective and non-competitive BACE1 inhibitory activity with low off-target inhibition of BACE2 and other aspartic and serine proteases. In addition, sulforaphane presented negative binding energy, suggesting that the compound had a high affinity for BACE1. It interacted with locations other than the active binding sites of BACE1 through van der Waals forces. Overall, sulforaphane appeared to be a promising candidate with potent and selective BACE1 inhibitory properties that play an important role in AD prevention. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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Review

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15 pages, 1907 KiB

Open AccessEditor’s ChoiceReview

Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Possible Therapeutic Role of Curcumin

by Ryszard Pluta, Wanda Furmaga-Jabłońska, Sławomir Januszewski and Stanisław J. Czuczwar

Nutrients 2022, 14(2), 248; https://doi.org/10.3390/nu14020248 - 07 Jan 2022

Cited by 21 | Viewed by 3784

Abstract

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and [...] Read more.

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer’s disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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29 pages, 3260 KiB

Open AccessReview

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis

by Polina S. Goncharova, Tatiana K. Davydova, Tatiana E. Popova, Maxim A. Novitsky, Marina M. Petrova, Oksana A. Gavrilyuk, Mustafa Al-Zamil, Natalia G. Zhukova, Regina F. Nasyrova and Natalia A. Shnayder

Nutrients 2021, 13(11), 3804; https://doi.org/10.3390/nu13113804 - 26 Oct 2021

Cited by 12 | Viewed by 6780

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively [...] Read more.

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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19 pages, 1689 KiB

Open AccessReview

Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment

by Alexander Popescu and Monica German

Nutrients 2021, 13(7), 2206; https://doi.org/10.3390/nu13072206 - 27 Jun 2021

Cited by 18 | Viewed by 18981

Abstract

Recent studies have highlighted the importance of vitamin K2 (VK2) in human health. However, there have been no clinical studies investigating the role of VK2 in the prevention or treatment of Alzheimer’s disease (AD), a debilitating disease for which currently there is no [...] Read more.

Recent studies have highlighted the importance of vitamin K2 (VK2) in human health. However, there have been no clinical studies investigating the role of VK2 in the prevention or treatment of Alzheimer’s disease (AD), a debilitating disease for which currently there is no cure. In reviewing basic science research and clinical studies that have connected VK2 to factors involved in AD pathogenesis, we have found a growing body of evidence demonstrating that VK2 has the potential to slow the progression of AD and contribute to its prevention. In our review, we consider the antiapoptotic and antioxidant effects of VK2 and its impact on neuroinflammation, mitochondrial dysfunction, cognition, cardiovascular health, and comorbidities in AD. We also examine the link between dysbiosis and VK2 in the context of the microbiome’s role in AD pathogenesis. Our review is the first to consider the physiological roles of VK2 in the context of AD, and, given the recent shift in AD research toward nonpharmacological interventions, our findings emphasize the timeliness and need for clinical studies involving VK2. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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16 pages, 890 KiB

Open AccessReview

The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases

by Tarek Benameur, Raffaella Soleti and Chiara Porro

Nutrients 2021, 13(4), 1318; https://doi.org/10.3390/nu13041318 - 16 Apr 2021

Cited by 37 | Viewed by 5016

Abstract

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an [...] Read more.

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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16 pages, 746 KiB

Open AccessReview

Myricetin as a Promising Molecule for the Treatment of Post-Ischemic Brain Neurodegeneration

by Ryszard Pluta, Sławomir Januszewski and Stanisław J. Czuczwar

Nutrients 2021, 13(2), 342; https://doi.org/10.3390/nu13020342 - 24 Jan 2021

Cited by 22 | Viewed by 3245

Abstract

The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding [...] Read more.

The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding the benefits of myricetin in post-ischemic neurodegeneration. The data in this article contribute to a better understanding of the potential benefits of myricetin in the treatment of post-ischemic brain neurodegeneration, and inform physicians, scientists and patients, as well as their caregivers, about treatment options. Due to the pleiotropic properties of myricetin, including anti-amyloid, anti-phosphorylation of tau protein, anti-inflammatory, anti-oxidant and autophagous, as well as increasing acetylcholine, myricetin is a promising candidate for treatment after ischemia brain neurodegeneration with full-blown dementia. In this way, it may gain interest as a potential substance for the prophylaxis of the development of post-ischemic brain neurodegeneration. It is a safe substance, commercially available, inexpensive and registered as a pro-health product in the US and Europe. Taken together, the evidence available in the review on the therapeutic potential of myricetin provides helpful insight into the potential clinical utility of myricetin in treating neurodegenerative disorders with full-blown dementia. Therefore, myricetin may be a promising complementary agent in the future against the development of post-ischemic brain neurodegeneration. Indeed, there is a scientific rationale for the use of myricetin in the prevention and treatment of brain neurodegeneration caused by ischemia. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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Other

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17 pages, 1161 KiB

Open AccessEditor’s ChoiceSystematic Review

Beneficial Effects of Spirulina Consumption on Brain Health

by Teresa Trotta, Chiara Porro, Antonia Cianciulli and Maria Antonietta Panaro

Nutrients 2022, 14(3), 676; https://doi.org/10.3390/nu14030676 - 05 Feb 2022

Cited by 21 | Viewed by 10900

Abstract

Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It is extensively utilized as a nutraceutical food supplement all over the world due to its high levels of functional compounds, such as phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating [...] Read more.

Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It is extensively utilized as a nutraceutical food supplement all over the world due to its high levels of functional compounds, such as phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating properties both in vivo and in vitro. Several scientific publications have suggested its positive effects in various pathologies such as cardiovascular diseases, hypercholesterolemia, hyperglycemia, obesity, hypertension, tumors and inflammatory diseases. Lately, different studies have demonstrated the neuroprotective role of Spirulina on the development of the neural system, senility and a number of pathological conditions, including neurological and neurodegenerative diseases. This review focuses on the role of Spirulina in the brain, highlighting how it exerts its beneficial anti-inflammatory and antioxidant effects, acting on glial cell activation, and in the prevention and/or progression of neurodegenerative diseases, in particular Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis; due to these properties, Spirulina could be considered a potential natural drug. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Therapeutic and Nutraceutical Applications in Neurodegeneration)

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