Benefits from Dietary Polyphenols for Brain Aging and Alzheimer’s Disease
TL;DR: This commentary discusses recent data on effects of curcumin, resveratrol and catechins on Alzheimer’s disease, particularly focusing on results of some epidemiological studies.
Abstract: Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease
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TL;DR: It is suggested that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases.
Abstract: Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.
3,370 citations
Cites background from "Benefits from Dietary Polyphenols f..."
...EGCG may also protect neurons by activating several signaling pathways, involving MAP kinases which are fundamental for cell survival.(90) The therapeutic role of catechins in Parkinson’s disease is also due to their ability to chelate iron....
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TL;DR: The need for increased regulation and guidelines for polyphenol consumption and supplementation is asserted in order to ensure consumers remain safe and informed about polyphenols.
Abstract: This narrative mini- review summarizes current knowledge of the role of polyphenols in health outcomes-and non-communicable diseases specifically-and discusses the implications of this evidence for public health, and for future directions for public health practice, policy, and research The publications cited originate mainly from animal models and feeding experiments, as well as human cohort and case-control studies Hypothesized protective effects of polyphenols in acute and chronic diseases, including obesity, neurodegenerative diseases, type 2 diabetes, and cardiovascular diseases, are evaluated Potential harmful effects of some polyphenols are also considered, counterbalanced with the limited evidence of harm in the research literature Recent international governmental regulations are discussed, as the safety and health claims of only a few specific polyphenolic compounds have been officially sanctioned The implications of food processing on the bioavailability of polyphenols are also assessed, in addition to the health claims and marketing of polyphenols as a functional food Finally, this mini-review asserts the need for increased regulation and guidelines for polyphenol consumption and supplementation in order to ensure consumers remain safe and informed about polyphenols
732 citations
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...EGCG may also protect neurons by activating cell survival signaling pathways (9)....
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TL;DR: This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.
Abstract: The oxidative stress imposed by reactive oxygen species (ROS) plays an important role in many chronic and degenerative diseases. As an important category of phytochemicals, phenolic compounds universally exist in plants, and have been considered to have high antioxidant ability and free radical scavenging capacity, with the mechanism of inhibiting the enzymes responsible for ROS production and reducing highly oxidized ROS. Therefore, phenolic compounds have attracted increasing attention as potential agents for preventing and treating many oxidative stress-related diseases, such as cardiovascular diseases, cancer, ageing, diabetes mellitus and neurodegenerative diseases. This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.
568 citations
TL;DR: A comprehensive review of studies on PCs with a focus on HDs seeks to find out why some PCs have received such considerable attention all over the world and shows that three countries most involved in research on PCs are USA, China, and India, and found that quercetin, catechin, and kaempferol are the three most studied PCs.
Abstract: “Let food be thy medicine and medicine be thy food” was expressed by Hippocrates more than 2000 years ago and the health benefits of natural food products have been considered for different goals s...
284 citations
TL;DR: Targeting of NF-κB signaling pathway could be a potent strategy for the prevention and/or treatment of human cancers and inflammatory diseases.
Abstract: The nuclear factor-kappaB (NF-kappaB) pathway is one of the most important cellular signal transduction pathways involved in both physiologic processes and disease conditions. It plays important roles in the control of immune function, inflammation, stress response, differentiation, apoptosis, and cell survival. Moreover, NF-kappaB is critically involved in the processes of development and progression of cancers. More importantly, recent studies have shown that NF-kappaB signaling also plays critical roles in the epithelial-mesenchymal transition (EMT) and cancer stem cells. Therefore, targeting of NF-kappaB signaling pathway could be a potent strategy for the prevention and/or treatment of human cancers and inflammatory diseases.
222 citations
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...By regulation of NF-κB, resveratrol also protects against vascular alterations, aging, and Alzheimer’s disease [130, 131]....
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References
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TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Abstract: The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
8,669 citations
TL;DR: The chapter discusses the metabolism of transition metals, such as iron and copper, and the chelation therapy that is an approach to site-specific antioxidant protection.
Abstract: Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.
5,033 citations
"Benefits from Dietary Polyphenols f..." refers background in this paper
...Markers of oxidative or nitrosative stress in biological specimens include protein carbonyls and 3-nitrotyrosine, for protein oxidation; thiobarbituric acidreactive substances (TBARS) and 4-hydroxy-2-transnonenal (HNE), for lipid peroxidation; 8-OH-20-deoxyguanosine and altered DNA, for DNA oxidation [2, 5]....
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...Additionally, the brain has high levels of ascorbate, which facilitate redox metals reactions [2]....
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TL;DR: These low molecular mass antioxidant molecules add significantly to the defense provided by the enzymes superoxide dismutase, catalase and glutathione peroxidases, which are termed ‘oxidative stress’.
Abstract: An imbalance between oxidants and antioxidants in favour of the oxidants, potentially leading to damage, is termed 'oxidative stress'. Oxidants are formed as a normal product of aerobic metabolism but can be produced at elevated rates under pathophysiological conditions. Antioxidant defense involves several strategies, both enzymatic and non-enzymatic. In the lipid phase, tocopherols and carotenes as well as oxy-carotenoids are of interest, as are vitamin A and ubiquinols. In the aqueous phase, there are ascorbate, glutathione and other compounds. In addition to the cytosol, the nuclear and mitochondrial matrices and extracellular fluids are protected. Overall, these low molecular mass antioxidant molecules add significantly to the defense provided by the enzymes superoxide dismutase, catalase and glutathione peroxidases.
4,485 citations
TL;DR: An overview of the nutritional effects of the main groups of polyphenolic compounds, including their metabolism, effects on nutrient bioavailability, and antioxidant activity, is offered, as well as a brief description of the chemistry ofpolyphenols and their occurrence in plant foods.
Abstract: Polyphenols constitute one of the most numerous and ubiquitous groups of plant metabolites and are an integral part of both human and animal diets. Ranging from simple phenolic molecules to highly polymerized compounds with molecular weights of greater than 30,000 Da, the occurrence of this complex group of substances in plant foods is extremely variable. Polyphenols traditionally have been considered antinutrients by animal nutritionists, because of the adverse effect of tannins, one type of polyphenol, on protein digestibility. However, recent interest in food phenolics has increased greatly, owing to their antioxidant capacity (free radical scavenging and metal chelating activities) and their possible beneficial implications in human health, such as in the treatment and prevention of cancer, cardiovascular disease, and other pathologies. Much of the literature refers to a single group of plant phenolics, the flavonoids. This review offers an overview of the nutritional effects of the main groups of polyphenolic compounds, including their metabolism, effects on nutrient bioavailability, and antioxidant activity, as well as a brief description of the chemistry of polyphenols and their occurrence in plant foods.
3,821 citations
"Benefits from Dietary Polyphenols f..." refers background or result in this paper
...It has also been suggested that the potential of polyphenols to form complexes with metal cations might interfere with the intestinal absorption of iron or copper, thus reducing their bioavailability, although data on this issue are divergent [ 21 ]....
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...The chemical antioxidant activity of polyphenols is correlated with the number of hydroxyl groups present on the aromatic A and B rings, and with the presence of a C2‐ C3 double bond (see Fig. 1): the most active ones contain between 3 and 6 hydroxyl groups [20, 21 ]....
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TL;DR: The nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain‐breaking antioxidants.
Abstract: Radicals are species containing one or more unpaired electrons. The oxygen radical superoxide (O 2 - ) and the non-radical oxidants hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) are produced during normal metabolism and perform several useful functions. Excessive production of O 2 - and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxy 1 radical (· OH) and other oxidants in the presence of “catalytic” iron or copper ions. A major form of antioxidant defence is the storage and transport of iron or copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e. g., by ischaemia or trauma, can cause increased iron availability and accelerate free radical reactions. This may be especially important in the brain, since areas of this organ are rich in iron and cerebrospinal fluid cannot bind released iron ions. Oxidative stress upon nervous tissue can produce damage by several interacting mechanisms, including rises in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminium and in damage to the substantia nigra in Parkinson’s disease are reviewed. Finally, the nature of antioxidants is discussed, with a suggestion that antioxidant enzymes and chelators of iron ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be taken in the design of antioxidants for therapeutic use.
2,968 citations
"Benefits from Dietary Polyphenols f..." refers background in this paper
...Compared to the other tissues, brain has higher probability to be challenged by ROS, because it consumes more than 20% of all the oxygen utilized by the other organs during mitochondrial respiration; moreover specific reactions, such those catalysed by monoamine oxidases, produce H2O2 and neurotransmitters themselves autoxidize and generate ROS [1]....
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...In the brain, ROS can also act indirectly by enhancing the expression of inducible nitric oxide synthase (iNOS), and the action of constitutive neuronal NOS (nNOS) that increase the production of nitric oxide radical (NO), via the catalytic conversion of arginine to citrulline....
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...This process is related to ROS production, which act as signals to activate genes like iNOS, interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a) and nuclear factor kappa B (NFkB)....
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...Much evidence suggests that oxidative stress induced by reactive oxygen species (ROS) is involved in age-associated cognitive decline and neuronal loss in neurodegenerative Special issue article in honor of Dr. Anna Maria Giuffrida-Stella....
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...It has indeed been shown that highly reducing flavonoids may undergo auto-oxidation in air, yielding ROS [95]....
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