{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:41:28Z","timestamp":1776944488852,"version":"3.51.4"},"reference-count":107,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04138\/2013"],"award-info":[{"award-number":["UID\/DTP\/04138\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Slovene Research Agency","award":["P4-0121"],"award-info":[{"award-number":["P4-0121"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress and inflammation (e.g., cancer, and cardiovascular and neurodegenerative disorders). Neurodegenerative diseases are globally one of the main causes of death and represent an enormous burden in terms of human suffering, social distress, and economic costs. Recent data expanded on the initial antioxidant-based mechanism of polyphenols\u2019 action by showing that they are also able to modulate several cell-signaling pathways and mediators. The proposed benefits of polyphenols, either as protective\/prophylactic substances or as therapeutic molecules, may be achieved by the consumption of a natural polyphenol-enriched diet, by their use as food supplements, or with formulations as pharmaceutical drugs\/nutraceuticals. It has also been proved that the health effects of polyphenols depend on the consumed amount and their bioavailability. However, their overconsumption may raise safety concerns due to the accumulation of high levels of these molecules in the organism, particularly if we consider the loose regulatory legislation regarding the commercialization and use of food supplements. This review addresses the main beneficial effects of food polyphenols, and focuses on neuroprotection and the safety issues related to overconsumption.<\/jats:p>","DOI":"10.3390\/antiox9010061","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T10:20:29Z","timestamp":1578651629000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":235,"title":["Polyphenols from Food and Natural Products: Neuroprotection and Safety"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-9357","authenticated-orcid":false,"given":"Rui F. M.","family":"Silva","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) and Department of Biochemistry and Human Biology (DBBH), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1008-0633","authenticated-orcid":false,"given":"Lea","family":"Poga\u010dnik","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, SI-1000 Ljubljana, Slovenia"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1753-4887.1998.tb01670.x","article-title":"Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance","volume":"56","author":"Bravo","year":"1998","journal-title":"Nutr. Rev."},{"key":"ref_2","first-page":"348","article-title":"Polyphenols, dietary sources and bioavailability","volume":"43","author":"Filesi","year":"2007","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/ajcn\/79.5.727","article-title":"Polyphenols: Food sources and bioavailability","volume":"79","author":"Manach","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1021\/jf0108765","article-title":"Antioxidant activities of pomegranate fruit extract and its anthocyanidins: Delphinidin, cyanidin, and pelargonidin","volume":"50","author":"Noda","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/mnfr.200700002","article-title":"Berry anthocyanins as novel antioxidants in human health and disease prevention","volume":"51","author":"Yasmin","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s12192-016-0695-3","article-title":"Curcumin exerts anti-inflammatory and antioxidative properties in 1-methyl-4-phenylpyridinium ion (MPP(+))-stimulated mesencephalic astrocytes by interference with TLR4 and downstream signaling pathway","volume":"21","author":"Yu","year":"2016","journal-title":"Cell Stress Chaperones"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/j.1471-4159.2006.03680.x","article-title":"Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin","volume":"96","author":"Fernandes","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1016\/j.fct.2011.07.006","article-title":"Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage","volume":"49","author":"Abib","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jnutbio.2015.10.003","article-title":"EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-kappaB target genes in human endothelial cells","volume":"28","author":"Liu","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.nbd.2006.08.006","article-title":"Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Hartman","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21519","DOI":"10.1002\/jcp.28777","article-title":"Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies","volume":"234","author":"Afshari","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Poti, F., Santi, D., Spaggiari, G., Zimetti, F., and Zanotti, I. (2019). Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020351"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1038\/ejcn.2010.221","article-title":"Identification of the 100 richest dietary sources of polyphenols: An application of the Phenol-Explorer database","volume":"64","author":"Neveu","year":"2010","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1080\/09637486.2017.1285870","article-title":"Dietary sources of polyphenols in the Mediterranean healthy Eating, Aging and Lifestyle (MEAL) study cohort","volume":"68","author":"Godos","year":"2017","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.nut.2019.03.005","article-title":"Adherence to a Mediterranean Dietary Pattern status and associated factors among Portuguese older adults: Results from the Nutrition UP 65 cross-sectional study","volume":"65","author":"Teixeira","year":"2019","journal-title":"Nutrition"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.drudis.2014.10.017","article-title":"New drugs from ancient natural foods. Oleocanthal, the natural occurring spicy compound of olive oil: A brief history","volume":"20","author":"Scotece","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1007\/s00394-015-0950-x","article-title":"Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study","volume":"55","author":"Knaze","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.nut.2014.04.012","article-title":"Estimated dietary intake and major food sources of polyphenols in the Polish arm of the HAPIEE study","volume":"30","author":"Grosso","year":"2014","journal-title":"Nutrition"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.numecd.2012.10.008","article-title":"Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: The PREDIMED study","volume":"23","author":"Covas","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.2174\/1381612824666181106091303","article-title":"Polyphenols: Plant Sources and Food Industry Applications","volume":"24","author":"Marranzano","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1080\/10408398.2018.1477730","article-title":"Understanding the potential benefits of thyme and its derived products for food industry and consumer health: From extraction of value-added compounds to the evaluation of bioaccessibility, bioavailability, anti-inflammatory, and antimicrobial activities","volume":"59","author":"Lorenzo","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_22","unstructured":"Patel, S.S., Acharya, A., Ray, R.S., Agrawal, R., Raghuwanshi, R., and Jain, P. (2019). Cellular and molecular mechanisms of curcumin in prevention and treatment of disease. Crit. Rev. Food Sci. Nutr., 1\u201353."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/s11255-019-02165-7","article-title":"Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126\/Akt-p53-p21 pathways","volume":"51","author":"Cao","year":"2019","journal-title":"Int. Urol. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Carrasco-Pozo, C., Cires, M.J., and Gotteland, M. (2019). Quercetin and Epigallocatechin Gallate in the Prevention and Treatment of Obesity: From Molecular to Clinical Studies. J. Med. Food, 22.","DOI":"10.1089\/jmf.2018.0193"},{"key":"ref_25","first-page":"7","article-title":"Challenges in neurodegeneration research","volume":"1","author":"Noble","year":"2010","journal-title":"Front. Psych."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0006-8993(03)03197-4","article-title":"Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death","volume":"986","author":"Lee","year":"2003","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1046\/j.1471-4159.2003.01976.x","article-title":"Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: Implications for the prevention and therapeutics of Alzheimer\u2019s disease","volume":"87","author":"Ono","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jnutbio.2004.05.002","article-title":"Neurological mechanisms of green tea polyphenols in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"15","author":"Weinreb","year":"2004","journal-title":"J. Nutr. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cell.2010.02.016","article-title":"Mechanisms underlying inflammation in neurodegeneration","volume":"140","author":"Glass","year":"2010","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Van Bulck, M., Sierra-Magro, A., Alarcon-Gil, J., Perez-Castillo, A., and Morales-Garcia, J.A. (2019). Novel Approaches for the Treatment of Alzheimer\u2019s and Parkinson\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030719"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.2174\/1570159X14666151208112754","article-title":"Current Treatment Options for Alzheimer\u2019s Disease and Parkinson\u2019s Disease Dementia","volume":"14","author":"Szeto","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1365-2567.2009.03225.x","article-title":"Inflammation in neurodegenerative diseases","volume":"129","author":"Amor","year":"2010","journal-title":"Immunology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cger.2009.12.003","article-title":"Potential future neuroprotective therapies for neurodegenerative disorders and stroke","volume":"26","author":"Tarawneh","year":"2010","journal-title":"Clin. Geriatr. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s11064-006-9203-y","article-title":"Redox regulation of cellular stress response in aging and neurodegenerative disorders: Role of vitagenes","volume":"32","author":"Calabrese","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12640-016-9600-1","article-title":"Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases","volume":"30","author":"Costa","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3945\/an.114.007500","article-title":"Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases","volume":"6","author":"Solanki","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/164456a0","article-title":"Antibacterial action of curcumin and related compounds","volume":"164","author":"Schraufstatter","year":"1949","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0891-5849(01)00803-6","article-title":"The \u201cFrench Paradox\u201d and beyond: Neuroprotective effects of polyphenols","volume":"32","author":"Sun","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fnagi.2014.00095","article-title":"Resveratrol and Alzheimer\u2019s disease: Message in a bottle on red wine and cognition","volume":"6","author":"Granzotto","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/ptr.4734","article-title":"Resveratrol protects cortical neurons against microglia-mediated neuroinflammation","volume":"27","author":"Zhang","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/mnfr.200500156","article-title":"Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders","volume":"50","author":"Mandel","year":"2006","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12035-013-8491-x","article-title":"Involvement of alpha7 nAChR signaling cascade in epigallocatechin gallate suppression of beta-amyloid-induced apoptotic cortical neuronal insults","volume":"49","author":"Zhang","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9701","DOI":"10.18632\/oncotarget.3832","article-title":"EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells","volume":"6","author":"Lee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.phrs.2015.12.027","article-title":"Epigallocatechin gallate and mitochondria-A story of life and death","volume":"104","author":"Oliveira","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.brainres.2016.09.020","article-title":"Potential for brain accessibility and analysis of stability of selected flavonoids in relation to neuroprotection in vitro","volume":"1651","author":"Pogacnik","year":"2016","journal-title":"Brain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.foodchem.2013.10.095","article-title":"Flavonoid metabolites transport across a human BBB model","volume":"149","author":"Faria","year":"2014","journal-title":"Food Chem."},{"key":"ref_47","unstructured":"Ulusoy, H.G., and Sanlier, N. (2019). A minireview of quercetin: From its metabolism to possible mechanisms of its biological activities. Crit. Rev. Food Sci. Nutr., 1\u201314."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fphar.2018.00422","article-title":"Anti-Parkinson Potential of Silymarin: Mechanistic Insight and Therapeutic Standing","volume":"9","author":"Ullah","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8337","DOI":"10.1038\/s41598-018-26645-5","article-title":"Oleuropein aglycone stabilizes the monomeric alpha-synuclein and favours the growth of non-toxic aggregates","volume":"8","author":"Palazzi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s12640-018-9869-3","article-title":"Naringenin Decreases alpha-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson\u2019s Disease Model in Mice","volume":"33","author":"Mani","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcn.2018.09.002","article-title":"Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in beta-amyloid overexpressing mice","volume":"93","author":"Gray","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1159\/000105477","article-title":"Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury","volume":"29","author":"West","year":"2007","journal-title":"Dev. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1007\/s11064-018-2586-8","article-title":"Resveratrol Boosts Cognitive Function by Targeting SIRT1","volume":"43","author":"Cao","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/1440-1681.13105","article-title":"Resveratrol alleviates nuclear factor-kappaB-mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischemia-reperfusion via suppressing endoplasmic reticulum stress","volume":"46","author":"Pan","year":"2019","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fncel.2013.00281","article-title":"Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma","volume":"7","author":"Menard","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.foodres.2017.07.026","article-title":"Green tea supplementation produces better neuroprotective effects than red and black tea in Alzheimer-like rat model","volume":"100","author":"Schimidt","year":"2017","journal-title":"Food Res. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/glia.20954","article-title":"Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts","volume":"58","author":"Willis","year":"2010","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.foodchem.2016.07.128","article-title":"Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation","volume":"215","author":"Garcia","year":"2017","journal-title":"Food Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1002\/jnr.21205","article-title":"Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia","volume":"85","author":"Lau","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2174\/138161212798918995","article-title":"Curcumin: A potential neuroprotective agent in Parkinson\u2019s disease","volume":"18","author":"Mythri","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tili, E., and Michaille, J.J. (2016). Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs. Molecules, 21.","DOI":"10.3390\/molecules21091263"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s40495-015-0018-x","article-title":"\u201cCurcumin, the King of Spices\u201d: Epigenetic Regulatory Mechanisms in the Prevention of Cancer, Neurological, and Inflammatory Diseases","volume":"1","author":"Boyanapalli","year":"2015","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_63","first-page":"89","article-title":"Environmental Enrichment, Age, and PPARalpha Interact to Regulate Proliferation in Neurogenic Niches","volume":"10","author":"Rivera","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"366","DOI":"10.4103\/1673-5374.202926","article-title":"Dysregulation of neurogenesis by neuroinflammation: Key differences in neurodevelopmental and neurological disorders","volume":"12","author":"Fan","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Szwajgier, D., Borowiec, K., and Pustelniak, K. (2017). The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action. Nutrients, 9.","DOI":"10.3390\/nu9050477"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3945\/ajcn.115.124545","article-title":"Dietary flavonoid intake and risk of incident depression in midlife and older women","volume":"104","author":"Chang","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Godos, J., Castellano, S., Ray, S., Grosso, G., and Galvano, F. (2018). Dietary Polyphenol Intake and Depression: Results from the Mediterranean Healthy Eating, Lifestyle and Aging (MEAL) Study. Molecules, 23.","DOI":"10.3390\/molecules23050999"},{"key":"ref_68","first-page":"1487","article-title":"New concepts in nutraceuticals as alternative for pharmaceuticals","volume":"5","author":"Nasri","year":"2014","journal-title":"Int. J. Prev. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bcp.2018.07.050","article-title":"Polyphenols, food and pharma. Current knowledge and directions for future research","volume":"156","author":"Moreno","year":"2018","journal-title":"Biochem. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuint.2015.07.003","article-title":"Bioavailability of dietary polyphenols: Factors contributing to their clinical application in CNS diseases","volume":"89","author":"Pandareesh","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1039\/C3FO60702J","article-title":"A standardised static in vitro digestion method suitable for food\u2014An international consensus","volume":"5","author":"Minekus","year":"2014","journal-title":"Food Funct."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.foodchem.2010.08.036","article-title":"In vitro human digestion models for food applications","volume":"125","author":"Hur","year":"2011","journal-title":"Food Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/nprot.2010.76","article-title":"Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier","volume":"5","author":"Bernas","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10571-004-1377-8","article-title":"Permeability Studies on In Vitro Blood\u2013Brain Barrier Models: Physiology, Pathology, and Pharmacology","volume":"25","author":"Deli","year":"2005","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/NUA-2012-0005","article-title":"Flavonoid transport across blood-brain barrier: Implication for their direct neuroprotective actions","volume":"1","author":"Faria","year":"2012","journal-title":"Nutr. Aging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2478\/s11658-010-0006-4","article-title":"Flavonoid transport across RBE4 cells: A blood-brain barrier model","volume":"15","author":"Faria","year":"2010","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1471-4159.2011.07594.x","article-title":"Resveratrol mitigates lipopolysaccharide- and Abeta-mediated microglial inflammation by inhibiting the TLR4\/NF-kappaB\/STAT signaling cascade","volume":"120","author":"Capiralla","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s11064-010-0144-0","article-title":"Flavonoids and astrocytes crosstalking: Implications for brain development and pathology","volume":"35","author":"Nones","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuroscience.2017.08.030","article-title":"Epigallocatechin gallate induces extracellular degradation of amyloid beta-protein by increasing neprilysin secretion from astrocytes through activation of ERK and PI3K pathways","volume":"362","author":"Yamamoto","year":"2017","journal-title":"Neuroscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1007\/s11064-008-9697-6","article-title":"Role of nitric oxide synthases in Parkinson\u2019s disease: A review on the antioxidant and anti-inflammatory activity of polyphenols","volume":"33","author":"Aquilano","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12640-012-9332-9","article-title":"Therapeutic attenuation of neuroinflammation and apoptosis by black tea theaflavin in chronic MPTP\/probenecid model of Parkinson\u2019s disease","volume":"23","author":"Anandhan","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1021\/jp312573y","article-title":"Molecular mechanism of the inhibition of EGCG on the Alzheimer Abeta(1\u201342) dimer","volume":"117","author":"Zhang","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nm1263","article-title":"Caspase-independent cell death","volume":"11","author":"Kroemer","year":"2005","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-4827(02)00027-7","article-title":"Necrosis: A specific form of programmed cell death?","volume":"283","author":"Proskuryakov","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1016\/j.febslet.2005.03.052","article-title":"Proteolytic mechanisms in necrotic cell death and neurodegeneration","volume":"579","author":"Tavernarakis","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1089\/ars.2007.9.49","article-title":"Mechanisms of cell death in oxidative stress","volume":"9","author":"Ryter","year":"2007","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7880","DOI":"10.1038\/s41598-018-25901-y","article-title":"Paradoxical cardiotoxicity of intraperitoneally-injected epigallocatechin gallate preparation in diabetic mice","volume":"8","author":"Rasheed","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1111\/1750-3841.13745","article-title":"Safety Evaluation of Green Tea Polyphenols Consumption in Middle-aged Ovariectomized Rat Model","volume":"82","author":"Shen","year":"2017","journal-title":"J. Food Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.yrtph.2018.03.019","article-title":"The safety of green tea and green tea extract consumption in adults\u2014Results of a systematic review","volume":"95","author":"Hu","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.biopha.2018.08.031","article-title":"Safety evaluation, anti-oxidative and anti-inflammatory effects of subchronically dietary supplemented high dosing grape seed powder (GSP) to healthy rat","volume":"107","author":"Charradi","year":"2018","journal-title":"Biomed. Pharm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.yrtph.2017.04.004","article-title":"Lipid-soluble green tea extract: Genotoxicity and subchronic toxicity studies","volume":"86","author":"Liu","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.lfs.2016.07.021","article-title":"Polyphenols in dementia: From molecular basis to clinical trials","volume":"161","author":"Molino","year":"2016","journal-title":"Life Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.brainres.2008.02.107","article-title":"Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice","volume":"1214","author":"Arendash","year":"2008","journal-title":"Brain Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10787-015-0236-1","article-title":"Green tea polyphenols and their potential role in health and disease","volume":"23","author":"Afzal","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kelly, E., Vyas, P., and Weber, J.T. (2017). Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries. Molecules, 23.","DOI":"10.3390\/molecules23010026"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1039\/b802662a","article-title":"Dietary phenolics: Chemistry, bioavailability and effects on health","volume":"26","author":"Crozier","year":"2009","journal-title":"Nat. Prod. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/00032719.2014.979361","article-title":"Chemiluminescence Method for Evaluation of Antioxidant Capacities of Different Invasive Knotweed Species","volume":"49","author":"Pogacnik","year":"2016","journal-title":"Anal. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1093\/jn\/138.9.1615","article-title":"Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans","volume":"138","author":"Egert","year":"2008","journal-title":"J. Nutr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.3390\/ijms12095592","article-title":"Epigallocatechin-3-gallate (EGCG) for Clinical Trials: More Pitfalls than Promises?","volume":"12","author":"Mereles","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1093\/jn\/135.11.2582","article-title":"Anthocyanins exist in the circulation primarily as metabolites in adult men","volume":"135","author":"Kay","year":"2005","journal-title":"J. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.neuint.2015.07.002","article-title":"Quercetin in brain diseases: Potential and limits","volume":"89","author":"Dajas","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1016\/j.bbagen.2012.12.027","article-title":"Oxidized quercetin inhibits alpha-synuclein fibrillization","volume":"1830","author":"Zhu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jep.2012.06.011","article-title":"Evaluation of oral subchronic toxicity of Pu-erh green tea (camellia sinensis var. assamica) extract in Sprague Dawley rats","volume":"142","author":"Wang","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1016\/j.fct.2011.08.023","article-title":"Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity","volume":"49","author":"Johnson","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.fct.2013.06.037","article-title":"Sub-acute toxicity profile of a modified resveratrol supplement","volume":"59","author":"Sangeetha","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1007\/s13346-018-0570-0","article-title":"Curcumin-loaded self-nanomicellizing solid dispersion system: Part II: In vivo safety and efficacy assessment against behavior deficit in Alzheimer disease","volume":"8","author":"Parikh","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"258598","DOI":"10.1155\/2015\/258598","article-title":"Efficacy and safety of pomegranate medicinal products for cancer","volume":"2015","author":"Vlachojannis","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/1\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:04:23Z","timestamp":1760364263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/1\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,10]]},"references-count":107,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["antiox9010061"],"URL":"https:\/\/doi.org\/10.3390\/antiox9010061","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,10]]}}}