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Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer 2.0

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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 January 2022) | Viewed by 8150

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Prof. Dr. Elena Ibáñez

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Laboratory of Foodomics, CIAL, CSIC, Nicolas Cabrera 9, 28049 Madrid, Spain
Interests: biorefinery; green processes; sustainable processes; plants; algae; agricultural by-products; chemical characterization
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Alejandro Cifuentes

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Laboratory of Foodomics, CIAL, National Research Council of Spain (CSIC), Madrid, Spain
Interests: foodomics; metabolomics; molecular mechanisms; neuroprotection; sustainable biomass; advanced chemical characterization
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

At present, there exists an ever-growing interest in the potential health benefits that some food/natural components may confer. Amongst the different bioactivities studied related to the consumption of health-promoting food/natural components, their possible neuroprotective effect is gaining importance, due to the huge negative impact that neurodegenerative diseases (ND) have on society. Indeed, the possibility of finding some dietary/natural components, such as terpenes, alkaloids, carbohydrates, polyphenols, peptides, etc., that able to positively prevent ND has evolved in a research line of great significance. However, to date, the mechanisms through which their neuroprotective activities would be exerted are still under discussion and in many cases largely unknown in several ND, especially in the case of Alzheimer’s disease (AD). At present, AD is considered an incurable disease, and treatments are only focused on alleviating symptoms. For this reason, the prevention of the development of this disease is of utmost importance. In this regard, this Special Issue might be a very useful tool to discuss the neuroprotective effects of dietary/natural compounds at a molecular level against this pandemic illness. This Special Issue of International Journal of Molecular Sciences will contain both research and review papers by recognized experts in this field concerning various aspects related to the neuroprotective effect of food and natural bioactive compounds on different models of Alzheimer’s.

Prof. Dr. Elena Ibáñez
Prof. Dr. Alejandro Cifuentes
Guest Editors

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Keywords

Alzheimer
neurodegenerative disease
natural products
food ingredients
nutraceuticals
bioactive compounds
functional foods
neuroprotective effects
foodomics
green extraction
advanced analytical techniques

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Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer in International Journal of Molecular Sciences (7 articles)

Published Papers (9 papers)

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Research

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19 pages, 1630 KiB

Open AccessArticle

Selective Extraction of Piceatannol from Passiflora edulis by-Products: Application of HSPs Strategy and Inhibition of Neurodegenerative Enzymes

by Luana Cristina dos Santos, Jose Antonio Mendiola, Andrea del Pilar Sánchez-Camargo, Gerardo Álvarez-Rivera, Juliane Viganó, Alejandro Cifuentes, Elena Ibáñez and Julian Martínez

Int. J. Mol. Sci. 2021, 22(12), 6248; https://doi.org/10.3390/ijms22126248 - 10 Jun 2021

Cited by 12 | Viewed by 2857

Abstract

Passiflora edulis by-products (PFBP) are a rich source of polyphenols, of which piceatannol has gained special attention recently. However, there are few studies involving environmentally safe methods for obtaining extracts rich in piceatannol. This work aimed to concentrate piceatannol from defatted PFBP (d-PFBP) by means of pressurized liquid extraction (PLE) and conventional extraction, using the bio-based solvents selected with the Hansen solubility parameters approach. The relative energy distance (Ra) between solvent and solute was: Benzyl Alcohol (BnOH) < Ethyl Acetate (EtOAc) < Ethanol (EtOH) < EtOH:H₂O. Nonetheless, EtOH presented the best selectivity for piceatannol. Multi-cycle PLE at 110 °C was able to concentrate piceatannol 2.4 times more than conventional extraction. PLE exhibited a dependence on kinetic parameters and temperature, which could be associated with hydrogen bonding forces and the dielectric constant of the solvents. The acetylcholinesterase (AChE) and lipoxygenase (LOX) IC₅₀ were 29.420 μg/mL and 27.682 μg/mL, respectively. The results reinforce the demand for processes to concentrate natural extracts from food by-products. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer 2.0)

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12 pages, 1673 KiB

Open AccessArticle

Synergistic Neuroprotective Effect of Schisandra chinensis and Ribes fasciculatum on Neuronal Cell Death and Scopolamine-Induced Cognitive Impairment in Rats

by Eunkuk Park, Min Jeong Ryu, Nam Ki Kim, Mun Hyoung Bae, Youngha Seo, Jeonghyun Kim, Subin Yeo, Memoona Kanwal, Chun Whan Choi, Jun Young Heo and Seon-Yong Jeong

Int. J. Mol. Sci. 2019, 20(18), 4517; https://doi.org/10.3390/ijms20184517 - 12 Sep 2019

Cited by 19 | Viewed by 3260

Abstract

Mild cognitive impairment (MCI) is considered as a transitional stage between aging and Alzheimer’s disease. In the present study, we examined the protective effect of Schisandra chinensis (SC) and Ribes fasciculatum (RF) on neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley^® rats in vivo. A mixture of SC and RF extracts (SC+RF) significantly protected against hydrogen peroxide-induced PC12 neuronal cell death. The neuroprotective effect of SC+RF on scopolamine-induced memory impairment in rats was evaluated using the passive avoidance test and the Morris water maze test. In the passive avoidance test, SC+RF-treated rats showed an increased latency to escape, compared to the scopolamine-treated rats. Moreover, SC+RF treatment significantly reduced escape latency in water maze test, compared to treatment with scopolamine alone. To verify the long-term memory, we performed probe test of water maze test. As a result, rat treated with SC+RF spent more time in the target quadrant. Consistent with enhancement of memory function, the brain derived neurotrophic factor (BDNF) and its downstream molecules (pERK, pATK, and pCREB) are increased in SC+RF treatment in hippocampal area compared with scopolamine treated group. These results suggest that a mixture of SC and RF extracts may be a good therapeutic candidate for preventing mild cognitive impairment. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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17 pages, 7403 KiB

Open AccessArticle

Topographical Visualization of the Reciprocal Projection between the Medial Septum and the Hippocampus in the 5XFAD Mouse Model of Alzheimer’s Disease

by Sujin Kim, Yunkwon Nam, Yu-on Jeong, Hyun Ha Park, Seong-kyung Lee, Soo Jung Shin, Haram Jung, Byeong-Hyeon Kim, Sang Bum Hong, Yong Ho Park, Jihee Kim, Jaemin Yu, Doo-Han Yoo, Sun-Hyun Park, Seong Gak Jeon and Minho Moon

Int. J. Mol. Sci. 2019, 20(16), 3992; https://doi.org/10.3390/ijms20163992 - 16 Aug 2019

Cited by 22 | Viewed by 7825

Abstract

It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer’s disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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11 pages, 1859 KiB

Open AccessArticle

Preventive Effects of Tryptophan–Methionine Dipeptide on Neural Inflammation and Alzheimer’s Pathology

by Yasuhisa Ano, Yuka Yoshino, Kazuyuki Uchida and Hiroyuki Nakayama

Int. J. Mol. Sci. 2019, 20(13), 3206; https://doi.org/10.3390/ijms20133206 - 29 Jun 2019

Cited by 15 | Viewed by 3622

Abstract

Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan–tyrosine (WY) and tryptophan–methionine (WM) peptides as the suppressants of activation of the primary microglia and showed that WY peptide consumption suppresses inflammation in the brains of Alzheimer’s disease model mice. However, the effects of the WM peptide on inflammation in the brain and Alzheimer’s pathology have not been investigated. Here, we evaluated the effect of WM peptide consumption on Alzheimer’s disease model (5×FAD) mice. In 5×FAD mice, intake of WM peptide suppressed the production of inflammatory cytokines, activation of microglia, and infiltration of activated microglia around β amyloid (Aβ) depositions. WM peptide intake reduced Aβ deposition in the cortex and hippocampus and then improved the object recognition memory. Taken together with previous reports, the current findings indicate that ingestion of tryptophan-related peptides or food material rich in tryptophan-related peptides, thereby regulating microglial activity, represents a potential preventive approach for cognitive decline and dementia related to inflammation. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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20 pages, 4021 KiB

Open AccessArticle

Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease

by Soo Jung Shin, Seong Gak Jeon, Jin-il Kim, Yu-on Jeong, Sujin Kim, Yong Ho Park, Seong-Kyung Lee, Hyun Ha Park, Sang Bum Hong, Sua Oh, Ji-young Hwang, Hyeon soo Kim, HyunHee Park, Yunkwon Nam, Yong Yook Lee, Jwa-Jin Kim, Sun-Hyun Park, Jong-Seok Kim and Minho Moon

Int. J. Mol. Sci. 2019, 20(12), 3030; https://doi.org/10.3390/ijms20123030 - 21 Jun 2019

Cited by 45 | Viewed by 6748

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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Review

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36 pages, 1884 KiB

Open AccessReview

Activity of Selected Group of Monoterpenes in Alzheimer’s Disease Symptoms in Experimental Model Studies—A Non-Systematic Review

by Karolina Wojtunik-Kulesza, Monika Rudkowska, Kamila Kasprzak-Drozd, Anna Oniszczuk and Kinga Borowicz-Reutt

Int. J. Mol. Sci. 2021, 22(14), 7366; https://doi.org/10.3390/ijms22147366 - 08 Jul 2021

Cited by 17 | Viewed by 4456

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia and cognitive function impairment. The multi-faced character of AD requires new drug solutions based on substances that incorporate a wide range of activities. Antioxidants, AChE/BChE inhibitors, BACE1, or anti-amyloid platelet aggregation substances are most desirable because they improve cognition with minimal side effects. Plant secondary metabolites, used in traditional medicine and pharmacy, are promising. Among these are the monoterpenes—low-molecular compounds with anti-inflammatory, antioxidant, enzyme inhibitory, analgesic, sedative, as well as other biological properties. The presented review focuses on the pathophysiology of AD and a selected group of anti-neurodegenerative monoterpenes and monoterpenoids for which possible mechanisms of action have been explained. The main body of the article focuses on monoterpenes that have shown improved memory and learning, anxiolytic and sleep-regulating effects as determined by in vitro and in silico tests—followed by validation in in vivo models. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer 2.0)

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40 pages, 2044 KiB

Open AccessReview

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

by Sudip Dhakal, Naufal Kushairi, Chia Wei Phan, Benu Adhikari, Vikineswary Sabaratnam and Ian Macreadie

Int. J. Mol. Sci. 2019, 20(20), 5090; https://doi.org/10.3390/ijms20205090 - 14 Oct 2019

Cited by 57 | Viewed by 8261

Abstract

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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19 pages, 1023 KiB

Open AccessReview

Ketogenic Diet in Alzheimer’s Disease

by Marta Rusek, Ryszard Pluta, Marzena Ułamek-Kozioł and Stanisław J. Czuczwar

Int. J. Mol. Sci. 2019, 20(16), 3892; https://doi.org/10.3390/ijms20163892 - 09 Aug 2019

Cited by 170 | Viewed by 38673

Abstract

At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer’s disease. This review aims to examine the role of the ketogenic diet in Alzheimer’s disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer’s disease. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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21 pages, 934 KiB

Open AccessReview

Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer’s Disease

by Syed Haris Omar

Int. J. Mol. Sci. 2019, 20(11), 2797; https://doi.org/10.3390/ijms20112797 - 07 Jun 2019

Cited by 41 | Viewed by 13942

Abstract

The risk of Alzheimer’s disease (AD) increases with nonmodifiable conditions including age and lack of effective efficacious pharmacotherapy. During the past decades, the non-pharmacotherapy mode of treatment of dietary modification received extensive attention in AD research. In order to reduce the AD pathology and cognitive decline, various dietary patterns have been attempted including caloric restriction (CR), dietary approaches to stop hypertension (DASH), ketogenic diets (KD), Mediterranean diet (MedDi) and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet. Higher adherence to the MedDi diet was associated with decreases in cardiovascular and neurological disorders including AD and related cognitive decline. However, another emerging healthy dietary pattern MIND diet has also been associated with slower rates of cognitive decline and significant reduction of AD rate. Olive serves as one of the building block components of MedDi and MIND diets and the exerted potential health beneficial might be suggested due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). A few trials using medical food showed an optimal result in presymptomatic or early stages of AD. The review supports the notion that MedDi and MIND diets display potential for maintaining the cognitive function as nonpharmacological agents against AD pathology and proposed preventative mechanism through the presence of olive biophenols and presents the gaps along with the future directions. Full article

(This article belongs to the Special Issue Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer)

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