Polyphenols as an Effective Therapeutic Intervention Against Cognitive Decline During Normal and Pathological Brain Aging.
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.
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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
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
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
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
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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TL;DR: Abeta fibrils promote clustering of h-AbetaPP in abnormal focal adhesion-like structures that mediate neuronal dystrophy, increasing its association with the cytoskeleton and suggesting that AbetaPP may play a significant role in AD pathogenesis.
31 citations
TL;DR: Gallic acid is suggested as a promising nutraceutical for the management of Alzheimer’s disease by showing that gallic acid could ameliorate elevated ChEs and BACE-1 activities, as well as oxidative stress induced by β-amyloid generation in D. melanogaster model of AD.
Abstract: This study evaluated the effect of gallic acid on some selected biomarkers in Drosophila melanogaster model of Alzheimer’s disease (AD). Transgenic D. melanogaster expressing human amyloid precursor protein and β-secretase (BACE 1) genes were used as AD flies while wild type (Oregon strain) flies served as the normal control flies. Both fly strains were exposed to gallic acid in their diet. Thereafter, the flies were sacrificed and homogenized. The homogenates were assayed for reactive oxygen species (ROS), malondialdehyde (MDA) and total thiol contents, as well as the activity of catalase. Also the activity of cholinesterases (ChEs) and β-secretase (BACE-1) were quantified. Results showed that the AD flies had significantly higher ChEs and BACE-1 activity, ROS and MDA contents, as well as lower total thiol level and catalase activity compared to the normal control flies. However, these biochemical impairments in AD control flies were significantly ameliorated in AD flies treated with gallic acid. Therefore, this study has shown that gallic acid could ameliorate elevated ChEs and BACE-1 activities, as well as oxidative stress induced by β-amyloid generation in D. melanogaster model of AD. This therefore, suggests gallic acid as a promising nutraceutical for the management of AD.
30 citations
TL;DR: The results demonstrated that GSPE supplementation and swimming training either individually or in combination had an improvement on acquisition and working memory with reduced AChE activity in the medial prefrontal cortex (mPFC) and hippocampus (HC).
Abstract: Decline in cognition is one of the earliest signs of normal brain aging. Several dietary and non-pharmacological approaches have been tested to slow down this process. The aim of the present study was to assess the influence of grape seed proanthocyanidin extract (GSPE) either individually or in combination with swimming training on acetylcholine esterase activity (AChE) and m1 acetylcholine receptor (m1AChR) on the extent of cognitive decline with aging. The experimental protocol included the oral administration of GSPE (400 mg/kg body weight) for 14 weeks to 4 (adult) and 18-month-old (middle-aged) male Wistar rats along with swimming training. They were subjected to behavioral testing followed by biochemical and immunohistochemical analysis. The results demonstrated that GSPE supplementation and swimming training either individually or in combination had an improvement on acquisition and working memory with reduced AChE activity in the medial prefrontal cortex (mPFC) and hippocampus (HC). Immunohistochemical and qRT-PCR evaluation showed an increase in m1AChR protein and mRNA in the CA1 region of HC and also mPFC upon swimming training with GSPE treatment. These beneficial and synergistic effects of GSPE and swimming training are suggestive as interventions in modulating the cognitive function, with GSPE alone being more suitable for middle-aged individuals.
24 citations
TL;DR: Evidence that elevated Sirt1 levels and/or activity may not help, and could even adversely exacerbates demise, during events of acute neuronal damage or death is noted, however, sustained Sirt 1 activation will be beneficial in situations of chronic and long-term sub-lethal stresses, and the status of IGF-1 signaling may influence Sirt2 action in a context dependent manner.
Abstract: Sirt1, the class III histone deacetylase, is generally associated with increased life span and with a pro-survival effect in neurons stressed by pathological factors. Recent work, however, suggests that Sirt1 silencing could also promote neuronal survival. A possible reason suggested is Sirt1 silencing enhanced expression of both IGF-1 and IGF-1 receptor, signaling from which promotes survival. This work adds to the small but steady stream of findings that are diametrically opposite to the overwhelmingly large amount of evidence supporting a beneficial effect of sustaining or enhancing Sirt1 activity in neuronal injuries and diseases. We attempt to reconcile this discrepancy below by noting evidence that elevated Sirt1 levels and/or activity may not help, and could even adversely exacerbates demise, during events of acute neuronal damage or death. However, sustained Sirt1 activation will be beneficial in situations of chronic and long-term sub-lethal stresses, and the status of IGF-1 signaling may influence Sirt1 action in a context dependent manner.
20 citations
TL;DR: In this article, the antioxidant potential of grape seed extract GSE, blackseed extract NSE and curcumin CUR was evaluated through determination of total soluble phenolic content and reducing power.
20 citations