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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549 citations
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527 citations
TL;DR: The results demonstrate that flavonoids are able to traverse the blood-brain barrier in vivo, however, the permeability of certain flavonoid in vivo is influenced by their lipophilicity and interactions with efflux transporters.
526 citations
TL;DR: Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions showed significant individual variation in change during the second follow-up.
515 citations
TL;DR: It is demonstrated that flavonoids and some metabolites are able to traverse the blood–brain barrier (BBB) and that the potential for permeation is consistent with compound lipophilicity.
Abstract: There is considerable current interest in the neuroprotective effects of flavonoids. This study focuses on the potential for dietary flavonoids, and their known physiologically relevant metabolites, to enter the brain endothelium and cross the blood-brain barrier (BBB) using well-established in vitro models (brain endothelial cell lines and ECV304 monolayers co-cultured with C6 glioma cells). We report that the citrus flavonoids, hesperetin, naringenin and their relevant in vivo metabolites, as well as the dietary anthocyanins and in vivo forms, cyanidin-3-rutinoside and pelargonidin-3-glucoside, are taken up by two brain endothelial cell lines from mouse (b.END5) and rat (RBE4). In both cell types, uptake of hesperetin and naringenin was greatest, increasing significantly with time and as a function of concentration. In support of these observations we report for the first time high apparent permeability (Papp) of the citrus flavonoids, hesperetin and naringenin, across the in vitro BBB model (apical to basolateral) relative to their more polar glucuronidated conjugates, as well as those of epicatechin and its in vivo metabolites, the dietary anthocyanins and to specific phenolic acids derived from colonic biotransformation of flavonoids. The results demonstrate that flavonoids and some metabolites are able to traverse the BBB, and that the potential for permeation is consistent with compound lipophilicity.
496 citations