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The major nutritional sources Flavonoids and brain health flavonoids include fruits, juices, vegetables, tea, cereals and wines Healthy blood sugar levels et al. Some common braln include Enhancing nutrient absorption, kaempferol flavonolsBalanced caffeine substitute, predominantly present Cancer prevention for children the onions, leeks and broccoli, fruits anc including Healthy eating habits and apigenin are abundant in celery and parsley.
Other common types of flavonoids include isoflavones daidzein, genisteinwhich are naturally distributed in soy and soy products, flavanones including naringenin and hesperetin, present in the citrus fruits and tomatoes. Flavanols, that are represented by epigallocatechin gallate EGCGcatechin, epicatechin and epigallocatechin are mainly sequestered in the green tea, red wine, and chocolate, whereas, anthocyanidins including malvidin, pelargonidin and cyanidinare are widely distributed in the berry fruits and red wine Manach et al.
Flavonoids are abundantly present as polyphenols in plants that are the products of secondary metabolites. The basic chemical structure of flavonoids contains two benzene rings A and C connected by a pyran ring B Figure 2.
One of the benzene ring A is fused with the pyran ring while the other benzene ring C is attached as substituent to the pyran ring. Depending upon the pattern of substitution of benzene rings, and that of substitution, oxidation and saturation of pyran ring, various derivatives of flavonoids can be synthesized that possess unique physicochemical properties and biological activities acceptable for the efficient management of neurodegenerative diseases.
Flavonoids are classified into various groups depending on the position at which the benzene ring C is attached to the pyran and the degree of unsaturation and oxidation of pyran ring. These different flavonoids have a dominant role in various pharmacological activities.
Each sub-type is discussed below. The class of flavonoids in which the benzene ring C is attached to the position 3 of the pyran ring is shown in Figure 3. Isoflavone are majorly found in various natural products especially soybean Wang and Murphy, Several researchers have also synthesized various derivatives of isoflavone by different synthetic approaches.
Wang in has synthesized various derivatives of isoflavones by Suzuki coupling Ding and Wang, Various derivatives of this famous group of easily biodegradable antioxidant have also been synthesized with triazin Jha et al.
Similarly, utilizing the catalytic approaches, including enzymatic or using a heterogeneous catalyst have been reported for efficient synthesis of isoflavone Kochs and Grisebach, ; Hoshino et al. The structures of some well-known isoflavones are given in Figure 3. In this class of flavonoids, the benzene ring C is attached to the position 4 of pyran ring.
The general structure of neoflavonoids is shown in Figure 2. Neoflavonoids, are naturally occurring heterocyclic compounds, mostly famous for their antidiabetic activity Donnelly and Boland, The neoflavonoids consist of neoflavones and neoflavenes. The most prominent source of neoflavonoids is natural but several researchers have also synthesized various analogs.
Some natural sources, from which the neoflavonoids are reported, are Echinop sniveus Singh and Pandey,Dalbergia odorifera Chan et al. The flavones contain a double bond on the pyran ring between position 2 and 3, and a carbonyl ketone at position 4.
Depending upon the taxonomic position of various plants, the flavones contain hydroxyl substituents at both the aromatic rings. Some commonly employed flavones from both the natural and synthetic origin are shown in Figure 4. The history of flavones from natural sources is very common since their synthetic history is also long Fukui et al.
Figure 4. The chemical structures of major flavones derived from natural and synthetic origin. Chemically, flavonols are the alcoholic derivatives of flavones. The flavonols differ from the flavones in the hydroxyl group at position 3 of pyran ring.
Generally, they can also be called as 3-hydroxyflavones. Mostly, the flavonols are synthesized by synthetic procedures.
A very well-known synthesis of flavonols is by oxidation and cyclization of chalcones which ends with 3-hydroxyflavonols. Figure 5 shows the various important flavonols.
In some cases, one or more hydrogen of hydroxyl group is replaced by a glucose moiety leading to a flavonol glycoside. As obvious from Figure 5 that pachypodol is not exactly a flavonol but its hydroxyl group is converted into a methoxy group.
However, due to its structure resemblance, it can be classified as a derivative of 3-hydroxyflavone, a flavonol.
The flavanones, saturated flavones, are also known as dihydroflavones. The only difference between flavones and flavanones is the absence of double bond between position 2 and 3. These types of compounds are shown in Figure 6. The flavanonols are the 3-hydroxy flavanones and are also called dihydroflavonols.
These are the flavonoids with saturated pyran ring having a hydroxyl group at position 3 and a carbonyl group at position 4. Some common examples of this class of flavonoids are shown in Figure 7.
The flavanols, also called flavanol are the types of flavonoids which lack the carbonyl group at position 4.
The pyran ring in these types of compounds is saturated and disubstituted at position 2 and 3. This property of the structure leads to four possible diastereomers of a flavanol.
In flavanols, the benzene ring C is attached to position 2 while the hydroxyl groups at position 3 of pyran ring. The structures of this type of flavonoids are shown in Figure 8. Of these, flavonoids not exactly fit in the definition of flavanol because of a lack of hydroxyl group at position 3.
But, still can be categorized under the heading of flavanols as it is structurally similar to other flavanol except the hydroxyl group at position 3. They are the only flavonoids which impart color. They are available in the cations form as chloride salts.
They are the salt derivatives of 2-phenylchromenylium flavylium cation. This group contains aurantinidin, capensinidin, cyaniding, delphinidin, europinidin, hirsutidin, malvidin, pelargonidin, peonidin, petunidin, pulchellidin and rosinidin.
All of them are different from each other on the basis of the attached groups denoted by R as shown in Figure 2. Although they do not have the pyran ring but are classified as flavonoids because of having a similar synthetic approach to flavonoids.
Moreover, in chalcones, the pyran moiety is available as open structure. The open structure has a carbonyl conjugated to a double bond making an α, β-unsaturated ring system, an ideal Michael acceptor for many organic reactions.
The structure of chalcone is shown in Figure 2. AD, a neurodegenerative disorder, which is characterized by a gradual memory loss, cognitive dysfunction, imperfection in the routine activities, and a decrease in the intellectual learning process Sadiq et al. It is estimated that Although, the exact etiology of AD is still not known, several mechanistic features including the deficiency of cholinesterases, deposition of β-amyloid plaques, hyperphosphorylation of tau proteins and generation of oxidative stress have been implicated in the development as well as progression of AD Kamal et al.
Due to the diverse nature of these pathological targets, the development of useful anti-AD drugs is still a challenging task for the scientific community. Currently, only five drugs have been marketed for the management of AD, among them four drugs including galantamine, tacrine, rivastigmine and donepezil are cholinesterase inhibitors whereas, the fifth one is the glutamatergic system modifier called memantine Ayaz et al.
No anti-amyloid drug is currently clinically available, though several agents are in the different phases of clinical trials Vassar, Due to the toxicity associated with the use of currently available drugs and their limited therapeutic effectiveness, the search for new anti-AD drugs is still underway Ayaz et al.
Consequently, the multi-targeting natural products based pure pharmacological moieties having more bio-safety and promising cognitive enhancing capabilities are among the potential therapeutic agents Baptista et al.
Flavonoids including epicatechingallate, gossypetin, quercetin and myricetin are reported to block β-amyloid, and tau aggregation, scavenge free radicals and sequester metal ions at clinically low concentrations Ono et al.
Furthermore, xanthone flavonoids have also been reported to scavenge the reactive oxygen species ROSinhibit MAO and AChE enzymes Zhang et al. Hence, flavonoids are a promising lead class of compounds for the efficient design and development of multipotent anti-AD drugs.
The amyloid precursor protein APP belongs to a group of transmembrane proteins having large extracellular domains Wasco et al. While members of the APP-like proteins family shares several extracellular domains like E1, E2; however, the amyloid beta Aβ domain is unique to the APP protein.
: Flavonoids and brain health| Can flavonoids help fend off forgetfulness? | Long-term administration of green tea catechins improves spatial cognition learning ability in rats. Hein, S. Systematic review of the effects of blueberry on cognitive performance as we age. A Biol. Hughes, R. Fueling gut microbes: a review of the interaction between diet, exercise, and the gut microbiota in athletes. Hurst, R. Consumption of an anthocyanin-rich extract made from New Zealand blackcurrants prior to exercise may assist recovery from oxidative stress and maintains circulating neutrophil function: a pilot study. Janle, E. Method for evaluating the potential of C 14 labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry. Methods Phys. B , — Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration. Food 13, — Jennings, A. The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis. Kashiwabara, M. Suppression of neuropeptide production by quercetin in allergic rhinitis model rats. BMC Complement Altern. Kern, T. Structured exercise alters the gut microbiota in humans with overweight and obesity-A randomized controlled trial. Obes 44, — Krikorian, R. Blueberry supplementation improves memory in older adults. Lau, F. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 miroglia. Lee, H. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Letenneur, L. Flavonoid intake and cognitive decline over a year period. Lila, M. Unraveling anthocyanin bioavailability for human health. Food Sci. Macready, A. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr. Mailing, L. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Sport Sci. Mancini, E. Green tea effects on cognition, mood and human brain function: a systematic review. Phytomedicine 34, 26— Manderino, L. Preliminary evidence for an association between the composition of the gut microbiome and cognitive function in neurologically healthy older adults. Manor, O. Health and disease markers correlate with gut microbiome composition across thousands of people. Martin, M. Impact of dietary flavanols on microbiota, immunity and inflammation in metabolic diseases. McGuire, S. Dietary supplementation with blueberry extract improves survival of transplanted dopamine neurons. McNamara, R. Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment. Aging 64, — Middleton, L. Changes in cognition and mortality in relation to exercise in late life: a population based study. PLoS One 3:e Miller, M. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Minghui, R. Risk Reduction of Cognitive Decline and Dementia. Geneva: World Health Organization. WHO guidelines. Moco, S. Metabolomics view on gut microbiome modulation by polyphenol-rich foods. Proteome Res. Morais, C. Anthocyanins as inflammatory modulators and the role of the gut microbiota. Mu, C. Gut microbiota: the brain peacekeeper. Napoli, N. Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Nasreddine, Z. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. Nieman, D. Exercise immunology: future directions. Sport Health Sci. Influence of a polyphenol-enriched protein powder on exercise-induced inflammation and oxidative stress in athletes: a randomized trial using a metabolomics approach. PLoS One 8:e Increased plasma levels of gut-derived phenolics linked to walking and running following two weeks of flavonoid supplementation. Immunometabolism: a multi-omics approach to interpreting the influence of exercise and diet on the immune system. Noble, E. Gut to brain dysbiosis: mechanisms linking Western diet consumption, the microbiome, and cognitive impairment. Novotny, M. Microbiome and cognitive impairment: can any diets influence learning processes in a positive way? Peet, R. The measurement of species diversity. Pereira-Caro, G. Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans. Free Radic. Piercy, K. Physical activity guidelines for Americans From the US department of health and human services. Outcomes e Rajaram, S. Plant-based dietary patterns, plant foods, and age-related cognitive decline. Rehfeld, K. Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly. PLoS One e Rooks, C. Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: a systematic review. Roopchand, D. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes 64, — Rovio, S. The effect of midlife physical activity on structural brain changes in the elderly. Aging 31, — Ruotolo, R. Saji, N. The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in japan. Santoro, A. Mediterranean diet and inflammaging in the elderly: the European project NU-AGE. Ageing Dev. Schell, J. Raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 diabetes. Scheperjans, F. Schlegel, P. Alzheimers Dis. Shukitt-Hale, B. The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Small, B. Rejuvenation Res. Socci, V. Enhancing human cognition with cocoa flavonoids. Sokolov, A. Chocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior. Spencer, J. Neuroinflammation: modulation by flavonoids and mechanisms of action. Aspects Med. Flavonoids and brain health: multiple effects underpinned by common mechanisms. Strathearn, K. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinsons disease. Brain Res. Tomas-Barberan, F. Interactions of gut microbiota with dietary polyphenols and consequences to human health. Metab Care 19, — Tooley, K. Effects of the human gut microbiota on cognitive performance, brain structure and function: a narrative review. Tsubaki, A. Changes in the laterality of oxygenation in the prefrontal cortex and premotor area during a min moderate-intensity cycling exercise. CrossRef Full Text Google Scholar. Tsukamoto, H. Flavanol-rich cocoa consumption enhances exercise-induced executive function improvements in humans. Nutrition 46, 90— Effect of exercise intensity and duration on post-exercise executive function. Tuohy, K. Department of Agriculture London: Pearson. United States Census Bureau Population Projections. Suitland, MA: US Census Bureau. Vauzour, D. Anthocyanins promote learning through modulation of synaptic plasticity related proteins in an animal model of ageing. Voss, M. Exercise, brain, and cognition across the life span. Wang, L. The potential role of phytonutrients flavonoids influencing gut microbiota in the prophylaxis and treatment of inflammatory bowel disease. Wang, Y. Reversals of age-related declines in neuronal signal transduction, cognitive and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. Kamal, Z. Anticholinesterse and antioxidant investigations of crude extracts, subsequent fractions, saponins and flavonoids of atriplex laciniata L. Katavic, P. Flavonoids as opioid receptor ligands: identification and preliminary Structure-activity relationships. Khan, H. Flavonoids as acetylcholinesterase inhibitors: current therapeutic standing and future prospects. Khan, M. Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies. Kochs, G. Enzymic synthesis of isoflavones. Kong, A. Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Kouhestani, S. Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia. Neural Regen. Kowaltowski, A. Mitochondria and reactive oxygen species. Krikorian, R. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Lau, F. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. Leclerc, S. A property common to most cyclin-dependent kinase inhibitors? Lee, B. Cells 30, — Lee, H. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J. Lee, J. Lee, S. Letenneur, L. Flavonoid intake and cognitive decline over a year period. Li, Q. Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Aβ 1—42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus. Neuroscience , — Lovell, M. Macready, A. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr. Maher, P. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Manach, C. Polyphenols: food sources and bioavailability. Bioavailability and bioefficacy of polyphenols in humans. Review of 97 bioavailability studies. Mandel, S. Simultaneous manipulation of multiple brain targets by green tea catechins: a potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS Neurosci. Multifunctional activities of green tea catechins in neuroprotection. Neurosignals 14, 46— Marder, M. GABA A -receptor ligands of flavonoid structure. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Markesbery, W. Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Mastroiacovo, D. Cocoa flavanol consumption improves cognitive function, blood pressure control and metabolic profile in elderly subjects: the Cocoa, Cognition and Aging CoCoA Study—a randomized controlled trial. Mecocci, P. Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease. Middleton, E. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. PubMed Abstract Google Scholar. Morel, I. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Müller, W. Nathan, C. Nordstedt, C. Ono, K. Onozuka, H. Orhan, I. Screening of various phenolic acids and flavonoid derivatives for their anticholinesterase potential. C 62, — Ovais, M. Phyto-Therapeutic and Nanomedicinal Approach to Cure Alzheimer Disease: Present Status and Future Opportunities. Pan, Y. Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats. Evidence for up-regulation of brain-derived neurotrophic factor mRNA by soy phytoestrogens in the frontal cortex of retired breeder female rats. Park, S. Park, L. Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Pasinetti, G. Development of a grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies. Patisaul, H. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. Qin, L. Protective effect of cyanidin 3-O-glucoside on β-amyloid peptide-induced cognitive impairment in rats. Resende, R. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Rezai-Zadeh, K. Green tea epigallocatechingallate EGCG reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. Reznichenko, L. Rice-Evans, C. Flavonoids in Health and Disease. Boca Raton, FL: CRC Press. Rinaldi, P. Aging 24, — Robak, J. Flavonoids are scavengers of superoxide anions. Sadiq, A. Schneider, L. Scholey, A. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. Schroeter, H. MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Aging 23, — Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase JNK , c-Jun and caspase Shimmyo, Y. Epigallocatechingallate and curcumin suppress amyloid β-induced β-site APP cleaving enzyme-1 upregulation. Neuroreport 19, — Shukitt-Hale, B. Blueberries and neuronal aging. Gerontology 58, — Effects of blackberries on motor and cognitive function in aged rats. Singh, M. Food Chem. Singh, R. Nivetin, a neoflavonoid from Echinops niveus. Phytochemistry 29, — Small, S. Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Socci, V. Enhancing human cognition with cocoa flavonoids. Spencer, J. The interactions of flavonoids within neuronal signalling pathways. Flavonoids: modulators of brain function? Flavonoids and brain health: multiple effects underpinned by common mechanisms. Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. The impact of fruit flavonoids on memory and cognition. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Sun, X. Neoflavonoids from Polygonum perfoliatum. Planta Med. Taniguchi, S. Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. Ullah, F. Phenolic, flavonoid contents, anticholinesterase and antioxidant evaluation of Iris germanica var; florentina. Uriarte-Pueyo, I. Flavonoids as acetylcholinesterase inhibitors. Vafeiadou, K. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. van Praag, H. Vassar, R. Alzheimers Res. Vauzour, D. Inhibition of the formation of the neurotoxin 5-S-cysteinyl-dopamine by polyphenols. Vepsäläinen, S. Vlahos, C. A specific inhibitor of phosphatidylinositol 3-kinase, 2- 4-morpholinyl phenyl-4Hbenzopyranone LY Voet, D. Serine Proteases Biochemistry p. Waltereit, R. Wang, J. Wang, D. Wang, H. Isoflavone content in commercial soybean foods. Wasco, W. Weinreb, O. Williams, C. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor BDNF levels. Williams, R. Flavonoids, cognition, and dementia: actions, mechanisms and potential therapeutic utility for Alzheimer disease. Flavonoids: antioxidants or signalling molecules? Yevchak, A. Promoting cognitive health and vitality: a review of clinical implications. Yin, Y. The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. U S A 99, — Zhang, K. Zhang, H. Multipotent antioxidants: from screening to design. Drug Discov Today 11, — Zheng, L. Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity. Citation: Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Ahmed J and Shahid M Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Received: 05 June ; Accepted: 11 June ; Published: 26 June Copyright © Ayaz, Sadiq, Junaid, Ullah, Ovais, Ullah, Ahmed and Shahid. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Export citation EndNote Reference Manager Simple TEXT file BibTex. Check for updates. REVIEW article. Introduction Flavonoids represent a diverse group of naturally occurring compounds which are biosynthesized from phenylalanine, and are ubiquitous to green pigments in the plant kingdom Havsteen, Methods Recent scientific literature published in high quality journals were collected using various search engines including Google Scholar, SciFinder, Science Direct, PubMed, Web of Science, EBSCO, Scopus, JSTOR and other web sources. Flavonoids Distribution in Nature Flavonoids represent a major group of secondary metabolites which are extensively distributed in nature especially in green plants. Figure 1. The major classes of flavonoids and their dietary sources. Figure 2. The chemical structures of major classes of flavonoids. Figure 3. The major isoflavones and their chemical structures. Figure 5. The major naturally occurring flavonols. Figure 6. The chemical structures of important isolated flavanones. Figure 7. This review will highlight the neuroprotective mechanisms of flavonoids and other polyphenols, in particular their ability interact with neuronal signalling pathways [ 91 , 97 ] and their potential to inhibit neuroinflammatory processes in the brain [ 17 , 48 ]. Flavonoids are major constituents of fruit, vegetables and beverages, such as wine, tea, cocoa and fruit juices. Most commonly, flavonoids share a common structure consisting of two aromatic rings A and B , which are bound together by three carbon atoms, forming an oxygenated heterocycle ring C Fig. The structures of the main classes of flavonoids. The major differences between the individual groups reside in the hydroxylation pattern of the ring-structure, the degree of saturation of the C-ring and the substitution of in the 3-position: a general structure of flavonoids, b structure of flavonols and flavones, c structure of flavanols, also referred as flavanols, d structure of anthocyanidins, e structure of flavanones and flavanonols and f structure of isoflavones. The flavanols, sometimes referred to as flavanols, are found predominantly in green and black teas, red wine and chocolate. Variations in their structures lie in the hydroxylation pattern of the B ring and the presence of gallic acid in position 3. The lack of a double bond at the 2—3 position and the presence of a 3-hydroxyl group on the C-ring create two centres of asymmetry. Typical dietary flavanols include catechin, epicatechin, epigallocatechin EGC and epigallocatechin gallate EGCG Fig. Flavanols exist also as oligomers or polymers, referred to as condensed tannins or proanthocyanidins, which are found in high concentration in cocoa, tea, red wine and fruits such as apples, grapes and strawberries. These differ in nature based on their constitutive units e. catechins and epicatechin , their sequence and the position of interflavanic linkages. The sources of anthocyanins such as pelargonidin, cyanidin and malvidin include red wine and berry fruits such as blueberries, blackberries cherries and strawberries. These compounds exist as glycosides in plants, are water-soluble and appear red or blue according to pH. Individual anthocyanins arise from the variation in number and arrangement of the hydroxyl and methoxy groups around the three rings Fig. Flavones such as apigenin, luteolin are found in parsley, chives, artichoke and celery. Hydroxylation on position 3 of the flavone structure gives rise to the 3-hydroxyflavones also known as the flavonols e. kaempferol, quercetin , which are found in onions, leeks, broccoli Fig. The diversity of these compounds stems from the varying positions of phenolic —OH groups around the three rings. Dietary flavanones include naringenin, hesperetin and taxifolin and are found predominantly in citrus fruit and tomatoes. Hydroxylation of flavanones in position 3 of C-ring gives rise to the flavanonols Fig. Finally, isoflavones such as daidzein and genistein are a subclass of the flavonoid family found in soy and soy products. They have a large structural variability and more than isoflavones have been identified to date and are classified according to oxidation level of the central pyran ring Fig. Although flavonoids have been identified as powerful antioxidants in vitro [ 84 — 86 ], their ability to act as antioxidants in vivo is limited by the extensive biotransformation and conjugation which occurs during their absorption from the gastrointestinal GI tract, in the liver and finally in cells reviewed in [ , ]. In the small intestine and liver, dietary flavonoids and other polyphenols are substrates for phase I hydrolysing and oxidizing and phase II conjugating and detoxifying , meaning that they are de-glucosylated and metabolised into glucuronides, sulphates and O -methylated derivatives [ 99 , , ]. Further metabolism occurs in the colon, where the enzymes of the gut microflora induce the breakdown of flavonoids to simple phenolics acids that may then undergo absorption and further metabolized in the liver [ 88 ]. Furthermore, flavonoids may undergo at least three types of intracellular metabolism: 1 Oxidative metabolism, 2 Prelated metabolism and 3 Conjugation with thiols, particularly GSH [ ]. Circulating metabolites of flavonoids, such as glucuronides, sulphates and conjugated O -methylated forms, or intracellular metabolites like flavonoid-GSH adducts, have significantly reduced antioxidant potential relative to the forms found in plants [ ]. Indeed, studies have indicated that although such conjugates and metabolites may participate antioxidant reactions and may scavenge reactive oxygen and nitrogen species in the circulation, their effectiveness to do so is reduced compared to their parent aglycones [ 22 , 70 , 94 , , ]. In order for flavonoids to access the brain, they must first cross the blood brain barrier BBB , which controls entry of xenobiotics into the brain [ 2 ]. Flavanones such as hesperetin, naringenin and their in vivo metabolites, along with some dietary anthocyanins, cyanidinrutinoside and pelargonidinglucoside, have been shown to traverse the BBB in relevant in vitro and in situ models [ ]. Their degree of BBB penetration is dependent on compound lipophilicity [ ], meaning that less polar O -methylated metabolites may be capable to greater brain uptake than the more polar flavonoid glucuronides. However, evidence exists to suggest that certain drug glucuronides may cross the BBB [ 1 ] and exert pharmacological effects [ 52 , ], suggesting that there may be a specific uptake mechanism for glucuronides in vivo. Their brain entry may also depend on their interactions with specific efflux transporters expressed in the BBB, such as P-glycoprotein [ 63 ] which appears to be responsible for the differences between naringenin and quercetin flux into the brain in situ [ ]. In animals, flavanones have been found to enter the brain following their intravenous administration [ 79 ], whilst epigallocatechin gallate [ ], epicatechin [ 3 ] and anthocyanins [ 26 , ] are found in the brain after their oral administration. Furthermore, several anthocyanins have been identified in different regions of the rat [ 78 ] and pig brains [ 47 ] of blueberry fed animals, with 11 intact anthocyanins found in the cortex and cerebellum. Studies have indicated that the accumulation of flavonoids in the brain is not dependent on the brain region, with levels of anthocyanins reaching 0. Flavanols have been shown to accumulate at significantly higher levels Hippocampus: 2. These results indicate that flavonoids traverse the BBB and are able to localize in the brain, suggesting that they are candidates for direct neuroprotective and neuromodulatory actions. There is a growing body of evidence to suggest that flavonoids may be able to counteract the neuronal injury underlying these disorders [ 68 , 98 , ]. Recent investigations have shown that 5-S-cysteinyl-catecholamine conjugates possess strong neurotoxicity and initiate a sustained increase in intracellular reactive oxygen species ROS in neurons leading to DNA oxidation, caspase-3 activation and delayed neuronal death [ 37 , ] Fig. In contrast, the inhibition afforded by flavanones, such as hesperetin, was not accompanied with the formation of cysteinyl-hesperetin adducts, indicating that it may inhibit via direct interaction with tyrosinase [ ]. Involvement of neuroinflammation, endogenous neurotoxins and oxidative stress in dopaminergic neurodegeneration. Structures of the 5-S-cysteinyl-dopamine 5-S-Cys-DA and the dihydrobenzothiazine-1 DHBT-1 are shown. Reactive oxygen and nitrogen species have also been proposed to play a role in the pathology of many neurodegenerative diseases [ 44 ] Fig. There is abundant evidence that flavonoids are effective in blocking this oxidant-induced neuronal injury, although their potential to do so is thought not to rely on direct radical or oxidant scavenging [ 98 , , ]. For example, flavonoids have been observed to block oxidative-induced neuronal damage by preventing the activation of caspase-3, providing evidence in support of their potent anti-apoptotic action [ 91 , 92 , ]. Similarly, the flavone, baicalein, has been shown to significantly inhibit 6-hydroxydopamine-induced JNK activation and neuronal cell death and quercetin may suppress JNK activity and apoptosis induced by hydrogen peroxide [ 42 , ], 4-hydroxynonenal [ ] and tumour necrosis factor-alpha TNF-alpha [ 49 ]. Glial cells microglia and astrocytes activation leads to the production of cytokines and other inflammatory mediators which may contribute to the apoptotic cell death of neurons observed in many neurodegenerative diseases. In particular, increases in cytokine production interleukin-1β, IL-1β; tumor necrosis factor-alpha, TNF-α [ 50 ], inducible nitric oxide synthase iNOS and nitric oxide NO , and increased NADPH oxidase activation [ 4 ] all contribute to glial-induced neuronal death Fig. These events are controlled by MAPK signalling which mediate both the transcriptional and post-transcriptional regulation of iNOS and cytokines in activated microglia and astrocytes [ 9 , 69 ]. Whilst ibuprofen, a non-steroidal anti-inflammatory drug, has been shown to delay the onset of neurodegenerative disorders, such as Parkinson disease [ 14 ], the majority of existing drug therapies for neurodegenerative disorders has failed to prevent the underlying degeneration of neurons. Consequently, there is a desire to develop alternative strategies capable of preventing the progressive neuronal loss resulting from neuroinflammation. In this respect, fisetin inhibits p38 MAP kinase phosphorylation in LPS-stimulated BV-2 microglial cells [ ] and the flavone luteolin inhibits IL-6 production in activated microglia via inhibition of the JNK signalling pathway. The effects of flavonoids on these kinases may influence downstream pro-inflammatory transcription factors important in iNOS transcription. One of these, nuclear factor-Kappa B NF-κB , responds to p38 signalling and is involved in iNOS induction [ 8 ], suggesting that there is interplay between signalling pathways, transcription factors and cytokine production in determining the neuroinflammatory response in the CNS. However, flavonoids have also been shown to prevent transcription factor activation, with the flavonol quercetin able to suppress NF-κB, signal transducer and activator of transcription-1 STAT-1 and activating protein-1 AP-1 activation in LPS- and IFN-γ-activated microglial cells [ 17 ]. There is a growing interest in the potential of phytochemicals to improve memory, learning and general cognitive ability [ , ]. A recent prospective study aimed at examining flavonoid intake in relation to cognitive function and decline, has provided strong evidence that dietary flavonoid intake is associated with better cognitive evolution, i. the preservation of cognitive performance with ageing [ 59 ]. After adjustment for age, sex, and educational level, flavonoid intake was found to be associated with significantly better cognitive performance at baseline and with a significantly better evolution of the performance over time. In particular, subjects included in the two highest quartiles of flavonoid intake had better cognitive evolution than subjects in the lowest quartile and after 10 years follow-up, subjects with the lowest flavonoid intake had lost on average 2. Such data provides a strong indication that regular flavonoid consumption may have a positive effect on neuro-cognitive performance as we age. There has been much interest in the neuro-cognitive effects of soy isoflavones Fig. Isoflavone supplementation has been observed to have a favourable effect on cognitive function [ 13 ], particularly verbal memory, in postmenopausal women [ 51 ] and a 6 and week supplementation was observed to have a positive effect of frontal lobe function [ 27 ]. Furthermore, animal studies have also indicated that isoflavones are capable of improving cognitive function [ 58 , 64 , 77 ]. However, there is still uncertainty regarding their effects as some large intervention trials have reported that isoflavone supplementation does not lead to cognitive improvements [ 30 ]. The rationale behind the potential of isoflavones to exert positive effects on cognitive function is believed to lie primarily in their potential to mimic the actions and functions of oestrogens in the brain [ 10 ]. They may also be effective by affecting the synthesis of acetylcholine and neurotrophic factors such as brain-derived neurotrophic factor BDNF and nerve growth factor NGF in hippocampus and frontal cortex [ 75 , 76 ]. There is also extensive evidence that berries, in particular blueberries, are effective at reversing age-related deficits in motor function and spatial working memory [ 5 , 12 , 45 , 46 , ]. Blueberry appears to have a pronounced effect on short-term memory [ 82 ] and has also been shown to improve long-term reference memory following 8 weeks of supplementation. Tests using a radial arm maze have supported these findings and have provided further evidence for the efficacy of blueberries [ ]. Indeed, these have shown that improvements in spatial memory may emerge within 3 weeks, the equivalent of about 3 years in humans. The beneficial effects of flavonoid-rich foods and beverages on psychomotor activity in older animals have also been reported [ 95 , 96 ]. In addition to those with berries, animal studies with tea [ 15 ] and pomegranate juice [ 36 ], or pure flavonols such as quercetin, rutin [ 80 ] or fisetin [ 66 ] have provided further evidence that dietary flavonoids are beneficial in reversing the course of neuronal and behavioural aging. The flavonoid-rich plant extract, Ginkgo Biloba has also been shown to induce positive effects on memory, learning and concentration [ 19 , 20 , 25 ]. Ginkgo Biloba has a prominent effect on brain activity and short-term memory in animals and humans suffering from cognitive impairment [ 43 , 93 , ] and promotes spatial learning in aged rodents [ 40 , , , ]. Furthermore, Ginkgo Biloba promotes inhibitory avoidance conditioning in rats with high-dose intake leading to short-term, but not long-term, passive avoidance learning in senescent mice [ , ]. However, the pharmacological mechanisms by which Ginkgo Biloba promotes cognitive effects are unclear, with its ability to elicit a reduction in levels of ROS [ 72 , 73 ], to increase cerebral blood flow [ 33 ], to modulate brain fluidity [ ], to interact with the muscarinic cholinergic system [ 18 ] and to protect the striatal dopaminergic system [ 81 ] all being suggested as possible mechanisms of brain action. The effects of flavonoid-rich foods on neuro-cognitive function have been linked to the ability of flavonoids to interact with the cellular and molecular architecture responsible for memory and learning [ , ], including those involved in long-term potentiation and synaptic plasticity [ 98 ] Fig. These effects are likely to lead to the enhanced neuronal connection and communication and thus a greater capacity for memory acquisition, storage and retrieval [ ]. For example, the flavanol - -epicatechin, especially in combination with exercise, has been observed to enhance the retention of rat spatial memory by a mechanism involving increased angiogenesis and neuronal spine density in the dentate gyrus of the hippocampus, and an up-regulation of genes associated with learning in the hippocampus [ ]. Fisetin, a flavonoid found in strawberries, has been shown to improve long-term potentiation and to enhance object recognition in mice by a mechanism dependent on the activation of ERK and CREB [ 66 ]. Signalling pathways underlying neuronal survival and cognitive performance. Flavonoids activate ERK-CREB pathway and the PI3 kinase-mTOR cascade leading to changes in synaptic plasticity. They are also capable of influencing neurogenesis through the activation of PI3 kinase-Akt-eNOS. The factors affecting dementia are age, hypertension, arteriosclerosis, diabetes mellitus, smoking, atrial fibrillation and those with the ApoE4 genotype [ 11 ]. There is evidence to suggest that flavonoids may be capable of preventing many forms of cerebrovascular disease, including those associated with stroke and dementia [ 21 , 23 ]. There is powerful evidence for the beneficial effects of flavonoids on endothelial function and peripheral blood flow [ 90 ] and these vascular effects are potentially significant as increased cerebrovascular function is known to facilitate adult neurogenesis in the hippocampus [ 32 ] Fig. Indeed, new hippocampal cells are clustered near blood vessels, proliferate in response to vascular growth factors and may influence memory [ 74 ]. As well as new neuronal growth, increases in neuronal spine density and morphology are considered vital for learning and memory [ 35 ]. Changes in spine density, morphology and motility have been shown to occur with paradigms that induce synaptic, as well as altered sensory experience, and lead to alterations in synaptic connectivity and strength between neuronal partners, affecting the efficacy of synaptic communication. These events are mediated at the cellular and molecular level and are strongly correlated with memory and learning. Efficient cerebral blood flow is also vital for optimal brain function, with several studies indicating that there is a decrease in cerebral blood flow CBF in patients with dementia [ 71 , 87 ]. For example, cerebral blood flow velocity is significantly lower in patients with Alzheimer disease and low CBF is also associated with incipient markers of dementia. In contrast, non demented subjects with higher CBF were less likely to develop dementia. Flavonoids have been shown to exert a positive effect on cerebral blood flow CBF in humans [ 29 , 31 ]. In support of these findings, an increase in cerebral blood flow through the middle cerebral artery has been reported after the consumption of flavanol-rich cocoa using TCD [ 29 ]. The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two common processes. Firstly, they interact with important neuronal signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and differentiation. It appears that the concentrations of flavonoids encountered in the brain may be sufficiently high to exert such pharmacological activity on receptors, kinases and transcription factors. Secondly, they are known to induce beneficial effects on the peripheral and cerebral vascular system, which lead to changes in cerebrovascular blood flow. Such changes are likely to induce angiogenesis, new nerve cell growth in the hippocampus and changes in neuronal morphology, all processes known to important in maintaining optimal neuronal function and neuro-cognitive performance Fig. The consumption of flavonoid-rich foods, such as berries and cocoa, throughout life holds a potential to limit neurodegeneration and prevent or reverse age-dependent deteriorations cognitive performance. However, at present the precise temporal nature of the effects of flavonoids on these events is unclear. For example, it is presently unclear as to when one needs to begin consuming flavonoids in order to obtain maximum benefits. It is also unclear which flavonoids are most effective in inducing these changes. However, due to the intense interest in the development of drugs capable of enhancing brain function, flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs. Aasmundstad TA, Morland J, Paulsen RE Distribution of morphine 6-glucuronide and morphine across the blood-brain barrier in awake, freely moving rats investigated by in vivo microdialysis sampling. J Pharmacol Exp Ther — PubMed CAS Google Scholar. Abbott NJ Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat — Abd El Mohsen MM, Kuhnle G, Rechner AR et al Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med — Google Scholar. Bal-Price A, Matthias A, Brown GC Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production. J Neurochem — Barros D, Amaral OB, Izquierdo I et al Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol Biochem Behav — Trends Mol Med — Bastianetto S, Zheng WH, Quirion R The Ginkgo biloba extract EGb protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C. Bhat NR, Feinstein DL, Shen Q et al p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. J Biol Chem — Bhat NR, Zhang P, Lee JC et al Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J Neurosci — Birge SJ Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? J Am Geriatr Soc — Neurobiol Aging — Casadesus G, Shukitt-Hale B, Stellwagen HM et al Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci — Casini ML, Marelli G, Papaleo E et al Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Fertil Steril — Casper D, Yaparpalvi U, Rempel N et al Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Neurosci Lett — Chan YC, Hosoda K, Tsai CJ et al Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. J Nutr Sci Vitaminol Tokyo — CAS Google Scholar. Am J Epidemiol — PubMed Google Scholar. Chen JC, Ho FM, Pei-Dawn LC et al Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol — Chopin P, Briley M Effects of four non-cholinergic cognitive enhancers in comparinson with tacrine and galanthamine on scopolamine-induced amnesia in rats. Psychopharmacology — Clostre F Gingko Biloba extract EGb State of knowledgement in the dawn of the year Ann Pharm Fr IS8—IS Cohen-Salmon C, Venault P, Martin B et al Effects of Ginkgo biloba extract EGb on learning and possible actions on aging. J Physiol Paris — Commenges D, Scotet V, Renaud S et al Intake of flavonoids and risk of dementia. Eur J Epidemiol — da Silva EL, Piskula MK, Yamamoto N et al Quercetin metabolites inhibit copper ion-induced lipid peroxidation in rat plasma. FEBS Lett — Am J Med — Neuroreport — Diamond BJ, Shiflett SC, Feiwel N et al Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil — El Mohsen MA, Marks J, Kuhnle G et al Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr — File SE, Hartley DE, Elsabagh S et al Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause — File SE, Jarrett N, Fluck E et al Eating soya improves human memory. Psychopharmacology Berl — |
| 7 servings of dark leafy greens a week may slow memory decline by 32% | Flavonoids and brain health Broccoli stuffed chicken Flavonoid antioxidants. Wasco, Heakth. Flavonoids and brain health Rev. Although animal ane suggest a beneficial impact of certain flavonols and their individual constituents on cognition, similar data from human studies are limited. Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment. Moderate-to-vigorous physical activity combined with flavonoid ingestion may improve post-exercise metabolic recovery Hurst et al. |
| Top bar navigation | Neurosci Lett — PubMed CAS Google Scholar Chan YC, Hosoda K, Tsai CJ et al Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. Always talk to your health care provider for diagnosis and treatment, including your specific medical needs. If fresh fruits aren't available, frozen berry mixes are a good alternative, Peterson said. Youdim KA, Dobbie MS, Kuhnle G et al Interaction between flavonoids and the blood-brain barrier: in vitro studies. Moreover, based on the extent of hydroxylation of aglycon, positions of the hydroxyl groups, saturation of pyran ring and differences in the derivatization of the hydroxyl groups are major differentiating features among the various classes of flavonoids. The factors affecting dementia are age, hypertension, arteriosclerosis, diabetes mellitus, smoking, atrial fibrillation and those with the ApoE4 genotype [ 11 ]. |
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