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Book ChapterDOI

Polyphenols as an Effective Therapeutic Intervention Against Cognitive Decline During Normal and Pathological Brain Aging.

01 Jan 2020-Advances in Experimental Medicine and Biology (Adv Exp Med Biol)-Vol. 1260, pp 159-174
TL;DR: A combined intervention of polyphenols along with regular physical exercise provides cognitive benefits for the aging brain and holds promising venues for preclinical and clinical studies in formulating neuro-nutraceuticals as functional foods for a healthy brain.
Abstract: Research in animals and humans has indicated that polyphenols can delay the age-related decline in learning, memory and neurodegenerative diseases. Among the polyphenols, berry phenolics have extensive beneficial effects because of their antioxidant and anti-inflammatory properties. Long-term consumption of grapes results in accumulation of polyphenols in the brain, which modulates cell-signalling pathways and neutralises the redox imbalance in the aging brain. Here we review the in vivo and in vitro evidence for considering grape-derived polyphenolics, the flavonoids- catechins, epicatechin, anthocyanidin, and quercetin, and non-flavonoids-gallic acid and resveratrol, as effective dietary sources to facilitate cognition in adults and lessen the decline in the old and pathogenic states, Alzheimer's and Parkinson's disease. Furthermore, a combined intervention of polyphenols along with regular physical exercise provides cognitive benefits for the aging brain and holds promising venues for preclinical and clinical studies in formulating neuro-nutraceuticals as functional foods for a healthy brain.
Citations
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01 Feb 2014
TL;DR: Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases that have traditionally been linked with calorie restriction and aging in mammals.
Abstract: Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases that have traditionally been linked with calorie restriction and aging in mammals. These proteins also play an important role in maintaining neuronal health during aging. During neuronal development, the SIR2 ortholog SIRT1 is structurally important, promoting axonal elongation, neurite outgrowth, and dendritic branching. This sirtuin also plays a role in memory formation by modulating synaptic plasticity. Hypothalamic functions that affect feeding behavior, endocrine function, and circadian rhythmicity are all regulated by SIRT1. Finally, SIRT1 plays protective roles in several neurodegenerative diseases including Alzheimer's, Parkinson's, and motor neuron diseases, which may relate to its functions in metabolism, stress resistance, and genomic stability. Drugs that activate SIRT1 may offer a promising approach to treat these disorders.

238 citations

Journal ArticleDOI
TL;DR: In this article, a phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin was used to mitigate brain fog in patients undergoing or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS).
Abstract: COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

81 citations

Journal ArticleDOI
TL;DR: Whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism is clearly documents.
Abstract: Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.

64 citations

Journal ArticleDOI
TL;DR: In this article , the authors investigated the neurotoxic effects of spike proteins in the brain and proposed a vaccine to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.
Abstract: SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.

53 citations

Journal ArticleDOI
TL;DR: In this paper, the effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways, and the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in poly-phenolic food, such as the diets of the Blue zones, are discussed.
Abstract: Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

34 citations

References
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Journal Article
TL;DR: Even a single dose of the Provinols™ was able to affect positively the space memory for limited time duration, and the improvement in space memory function and/or the positive role of attentional mechanisms may be taken into account mainly.
Abstract: OBJECTIVE: Several natural polyphenols exert effects upon the cardiovascular as well as nervous system. In vitro and animal studies suggest that polyphenols may potentially affect the human cognitive function. The aim was to study the effect of Provinols™, the polyphenolic compounds isolated from red wine, upon the human higher brain functions. MATERIAL AND METHODS: The accuracy of space memory was assessed by means of visually-guided and memory-guided saccadic eye movements. The EEG and blood pressure were registered also. The healthy undergraduates served as subjects. They were divided into the co ntrol, placebo and Provinols™ groups. The amplitudes of saccades, EEG spectral density, evoked potentials time-locked to saccadic onset and blood pressure were analyzed in control condition and 2 hours later, after administration of placebo, Provinols™ (4 mg/kg of body weight) or nothing. RESULTS: After the Provinols™ administration the memory-guided saccades were significantly more accurate and the significant decrease in the slow EEG bands, alpha power mainly, was registered over the broad regions of temporo-parietal cortex. No changes in saccadic eye movement related potentials as well as in blood pressure were found after the single dose Provinols™ administration. CONCLUSIONS: Even a single dose of the Provinols™ was able to affect positively the space memory for limited time duration. The improvement in space memory function and/or the positive role of attentional mechanisms may be taken into account mainly. More sensitive analysis of the particular participation of attentional and memory components demands the further study.

16 citations

Journal ArticleDOI
TL;DR: It is demonstrated that Rubus coreanus Miquel exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice and suggests that RCM may be a useful agent for improving memory impairment.
Abstract: The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results sug...

10 citations

Journal ArticleDOI
TL;DR: Daily supplementation with Concord grape juice was able to reverse the latent learning impairment normally seen in middle-aged male rats, most likely due to the presence of flavonoids in Concord grape Juice.
Abstract: ObjectiveTwo experiments were conducted to determine if dietary supplementation with Concord grape juice could reverse the latent learning impairment normally observed in middle-aged male rats.MethodsBoth experiments utilized the latent cue preference (LCP) task, in which water-replete rats sample water in one compartment of a three-compartment box, and are subsequently given a compartment preference test when water-deprived to determine if they remember the compartment cue previously associated with water. In the first experiment, 40 male Sprague-Dawley rats (9, 10, 11, or 12 months old) were used to determine the age of onset of the impairment. In the second experiment, 24 male Sprague-Dawley rats (11 months old) were given daily access (10 ml/day) to 50% Concord grape juice, 50% white grape juice, or a calorically-equivalent sugar solution daily for 5 weeks prior to training.ResultsThe first experiment revealed that the latent learning impairment begins to manifest at 10 months of age in the ma...

7 citations

Journal ArticleDOI
TL;DR: Rats under combined interventions displayed more alleviation of the age changes than rats with single interventions suggesting the possibilities of utilizing GSPE as a functional supplement in conjunction with swimming exercise towards improving neuronal survivability, and preventing cognitive decline beyond middle-age.

7 citations

Journal ArticleDOI
TL;DR: Even being a progressive syndrome, patients were able to relearn target vocabulary and strategies to improve sentence construction during the active phase of treatment, suggesting that linguistic-based treatment strategies may constitute an effective approach in the clinical management of PPA patients.
Abstract: Background:Language rehabilitation has been a valid strategy in order to slow the progression of symptoms and to increase quality of life for patients with primary progressive aphasia (PPA). The objective is to report the results of intensive short-term treatment administered to a case series of patients with non-fluent PPA (PPA-NF), semantic PPA (PPA-S), logopenic PPA (PPA-L) and unclassified PPA (PPANC), focusing on sentence production, lexical retrieval and working memory. Methods:Thirteen patients (5 PPA-S, 3 PPA-NF, 3 PPA-L and 2 PPA-NC) were submitted to a standardized training either targetting naming deficits (PPA-S and PPA-NC), sentence production or production of multisyllabic words (PPA-NF) and naming deficits or working memory (PPA-L and PPA-NC), based on principles of errorless learning. Thirty-minute rehabilitation sessions were offered twice a week, with daily workouts at home. The trained items (pre and post-treatment) and untrained items (pre and post-treatment) were compared. Generalization to other language tasks and functional communication was also informed. Follow-up results are reported for three patients. Results: The sample comprised 5 women and 8 men. Mean age was 65 years and mean schooling was 13.7 years. A significant improvement for treated items was seen for all patients. Nine patients also improved in untreated items. In addition, seven generalized for other tasks. Three patients were evaluated one month after the end of the treatment and demonstrated maintenance of treatment results. Conclusions: Even being a progressive syndrome, patients were able to relearn target vocabulary and strategies to improve sentence construction during the active phase of treatment. These preliminary results suggest that linguistic-based treatment strategies may constitute an effective approach in the clinical management of PPA patients.

1 citations