{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:15:03Z","timestamp":1760238903978,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"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":["iNOVA4Health - UID\/Multi\/04462\/2013","IF\/01097\/2013"],"award-info":[{"award-number":["iNOVA4Health - UID\/Multi\/04462\/2013","IF\/01097\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-KBBE-2013-613793"],"award-info":[{"award-number":["FP7-KBBE-2013-613793"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Scottish Government Rural and Environment Science and Analytical Services Division","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Plants are a reservoir of high-value molecules with underexplored biomedical applications. With the aim of identifying novel health-promoting attributes in underexplored natural sources, we scrutinized the diversity of (poly)phenols present within the berries of selected germplasm from cultivated, wild, and underutilized Rubus species. Our strategy combined the application of metabolomics, statistical analysis, and evaluation of (poly)phenols\u2019 bioactivity using a yeast-based discovery platform. We identified species as sources of (poly)phenols interfering with pathological processes associated with redox-related diseases, particularly, amyotrophic lateral sclerosis, cancer, and inflammation. In silico prediction of putative bioactives suggested cyanidin\u2013hexoside as an anti-inflammatory molecule which was validated in yeast and mammalian cells. Moreover, cellular assays revealed that the cyanidin moiety was responsible for the anti-inflammatory properties of cyanidin\u2013hexoside. Our findings unveiled novel (poly)phenolic bioactivities and illustrated the power of our integrative approach for the identification of dietary (poly)phenols with potential biomedical applications.<\/jats:p>","DOI":"10.3390\/antiox9090789","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:05:37Z","timestamp":1598432737000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-8480","authenticated-orcid":false,"given":"Regina","family":"Menezes","sequence":"first","affiliation":[{"name":"CEDOC, Chronic Diseases Research Centre, NOVA Medical School\/Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Alexandre","family":"Foito","sequence":"additional","affiliation":[{"name":"Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK"}]},{"given":"Carolina","family":"Jardim","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"In\u00eas","family":"Costa","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5362","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Garcia","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Rita","family":"Rosado-Ramos","sequence":"additional","affiliation":[{"name":"CEDOC, Chronic Diseases Research Centre, NOVA Medical School\/Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1784-2792","authenticated-orcid":false,"given":"Sabine","family":"Freitag","sequence":"additional","affiliation":[{"name":"Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4995-1678","authenticated-orcid":false,"given":"Colin James","family":"Alexander","sequence":"additional","affiliation":[{"name":"Biomathematics and Statistics Scotland, Invergowrie, Dundee DD2 5DA, UK"}]},{"given":"Tiago Fleming","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettinge, 37073 G\u00f6ttingen, Germany"},{"name":"Max Planck Institute for Experimental Medicine, 37075 G\u00f6ttingen, Germany"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-4265","authenticated-orcid":false,"given":"Derek","family":"Stewart","sequence":"additional","affiliation":[{"name":"Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK"},{"name":"School of Engineering and Physical Sciences, Institute of Mechanical, Process and Energy Engineering, Heriot-Watt University, Edinburgh EH14 4AS, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-1924","authenticated-orcid":false,"given":"Cl\u00e1udia N.","family":"Santos","sequence":"additional","affiliation":[{"name":"CEDOC, Chronic Diseases Research Centre, NOVA Medical School\/Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.cell.2015.11.031","article-title":"A New Golden Age of Natural Products Drug Discovery","volume":"163","author":"Shen","year":"2015","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural Products as Sources of New Drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrn1007","article-title":"Unfolding the role of protein misfolding in neurodegenerative diseases","volume":"4","author":"Soto","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10427","DOI":"10.1073\/pnas.0502066102","article-title":"Amyloid ion channels: A common structural link for protein-misfolding disease","volume":"102","author":"Quist","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-neuro-061010-113613","article-title":"Amyloid precursor protein processing and Alzheimer\u2019s disease","volume":"34","author":"Wong","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/ng.3043","article-title":"Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson\u2019s disease","volume":"46","author":"Nalls","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1073\/pnas.0509567103","article-title":"Lewy bodies","volume":"103","author":"Shults","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"DiFiglia","year":"1997","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1126\/science.1166066","article-title":"Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis","volume":"323","author":"Kwiatkowski","year":"2009","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.1165942","article-title":"Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6","volume":"323","author":"Vance","year":"2009","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s11101-017-9532-2","article-title":"BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits","volume":"17","author":"Dudnik","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1104\/pp.18.01074","article-title":"Identification and microbial production of the raspberry phenol salidroside that is active against Huntington\u2019s disease","volume":"179","author":"Kallscheuer","year":"2018","journal-title":"Plant Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fmolb.2019.00015","article-title":"Yeast Models for the Study of Amyloid-Associated Disorders and Development of Future Therapy","volume":"6","author":"DeRowe","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/j.1567-1364.2010.00658.x","article-title":"Yeast as a model for studying Alzheimer\u2019s disease","volume":"10","author":"Bharadwaj","year":"2010","journal-title":"FEMS Yeast Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.1090439","article-title":"Yeast cells provide insight into alpha-synuclein biology and pathobiology","volume":"302","author":"Outeiro","year":"2003","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.1090389","article-title":"Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein","volume":"302","author":"Willingham","year":"2003","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ju, S., Tardiff, D.F., Han, H., Divya, K., Zhong, Q., Maquat, L.E., Bosco, D.A., Hayward, L.J., Brown, R.H., and Lindquist, S. (2011). A yeast model of FUS\/TLS-dependent cytotoxicity. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1001052"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S0076-6879(05)07048-5","article-title":"Yeast screens for inhibitors of Ras-Raf interaction and characterization of MCP inhibitors of Ras-Raf interaction","volume":"407","author":"Khazak","year":"2006","journal-title":"Methods Enzym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiosc.2008.09.005","article-title":"Ethanol stress stimulates the Ca2+-mediated calcineurin\/Crz1 pathway in Saccharomyces cerevisiae","volume":"107","author":"Araki","year":"2009","journal-title":"J. Biosci. Bioeng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.15698\/mic2015.08.219","article-title":"From the baker to the bedside: Yeast models of Parkinson\u2019s disease","volume":"2","author":"Menezes","year":"2015","journal-title":"Microb. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/jnc.12271","article-title":"Harnessing the power of yeast to unravel the molecular basis of neurodegeneration","volume":"127","author":"Tenreiro","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.1245321","article-title":"Yeast reveal a \u201cdruggable\u201d Rsp5\/Nedd4 network that ameliorates alpha-synuclein toxicity in neurons","volume":"342","author":"Tardiff","year":"2013","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.1016\/j.ddtec.2012.02.003","article-title":"Phenotypic screens for compounds that target the cellular pathologies underlying Parkinson\u2019s disease","volume":"10","author":"Tardiff","year":"2013","journal-title":"Drug Discov. Today Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1016\/j.celrep.2018.11.028","article-title":"Inhibiting Stearoyl-CoA Desaturase Ameliorates alpha-Synuclein Cytotoxicity","volume":"25","author":"Vincent","year":"2018","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bbadis.2005.11.009","article-title":"A yeast-based model of alpha-synucleinopathy identifies compounds with therapeutic potential","volume":"1762","author":"Griffioen","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3233\/BR-2010-001","article-title":"Antioxidant and antiproliferative properties of strawberry tree tissues","volume":"1","author":"Tavares","year":"2010","journal-title":"J. Berry Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/yea.320070307","article-title":"Applications of high efficiency lithium acetate transformation of intact yeast cells using single-stranded nucleic acids as carrier","volume":"7","author":"Gietz","year":"1991","journal-title":"Yeast"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1101\/gad.11.24.3432","article-title":"Calcineurin acts through the CRZ1\/TCN1-encoded transcription factor to regulate gene expression in yeast","volume":"11","author":"Stathopoulos","year":"1997","journal-title":"Genes Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/ddv470","article-title":"Yeast reveals similar molecular mechanisms underlying alpha- and beta-synuclein toxicity","volume":"25","author":"Tenreiro","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"514","DOI":"10.4161\/auto.27707","article-title":"Detection of Saccharomyces cerevisiae Atg13 by western blot","volume":"10","author":"Cheong","year":"2014","journal-title":"Autophagy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/978-1-4939-3756-1_29","article-title":"High-Throughput Yeast-Based Reporter Assay to Identify Compounds with Anti-inflammatory Potential","volume":"1449","author":"Garcia","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_33","unstructured":"Miller, J. (1972). Experiments in Molecular Genetics, Cold Spring Harbor Laboratory."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11456","DOI":"10.1038\/s41598-017-11512-6","article-title":"Polyphenols journey through blood-brain barrier towards neuronal protection","volume":"7","author":"Figueira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0006-8993(96)00156-4","article-title":"beta-Amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity","volume":"720","author":"Ii","year":"1996","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"936","DOI":"10.7164\/antibiotics.51.936","article-title":"Identification of radicicol as an inhibitor of in vivo Ras\/Raf interaction with the yeast two-hybrid screening system","volume":"51","author":"Ki","year":"1998","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1074\/jbc.273.2.822","article-title":"Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway","volume":"273","author":"Soga","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19719","DOI":"10.3390\/molecules201119652","article-title":"Chemotaxonomic Metabolite Profiling of 62 Indigenous Plant Species and Its Correlation with Bioactivities","volume":"20","author":"Lee","year":"2015","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.redox.2017.03.027","article-title":"Protein aggregation into insoluble deposits protects from oxidative stress","volume":"12","author":"Carija","year":"2017","journal-title":"Redox Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s40880-016-0154-7","article-title":"A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS","volume":"35","author":"Pang","year":"2016","journal-title":"Chin. J. Cancer"},{"key":"ref_42","first-page":"83","article-title":"Targeting oncogenic BRAF in human cancer","volume":"355","author":"Pratilas","year":"2012","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1517\/14728222.2011.645805","article-title":"Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy","volume":"16","author":"Santarpia","year":"2012","journal-title":"Expert Opin. Targets"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nri3705","article-title":"Innate immune activation in neurodegenerative disease","volume":"14","author":"Heneka","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.2174\/1381612824666180515125926","article-title":"Metabolomics: A high-throughput screen for biochemical and bioactivity diversity in plants and crops","volume":"24","author":"Foito","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.biopha.2016.10.011","article-title":"Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions","volume":"84","author":"Suganthy","year":"2016","journal-title":"Biomed. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neurobiolaging.2016.12.024","article-title":"Quercetin-3-O-glucuronide promotes the proliferation and migration of neural stem cells","volume":"52","author":"Baral","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.hermed.2015.01.002","article-title":"Neuroprotective therapeutics from botanicals and phytochemicals against Huntington\u2019s disease and related neurodegenerative disorders","volume":"5","author":"Dey","year":"2015","journal-title":"J. Herb. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/BF00328503","article-title":"Branched-chain amino acids in the treatment of amyotrophic lateral sclerosis","volume":"236","author":"Testa","year":"1989","journal-title":"J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1212\/WNL.47.5.1220","article-title":"A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data","volume":"47","author":"Tandan","year":"1996","journal-title":"Neurology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"The Italian ALS Study Group (1993). Branched-chain amino acids and amyotrophic lateral sclerosis: A treatment failure. Neurology, 43, 2466\u20132470.","DOI":"10.1212\/WNL.43.12.2466"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0140-6736(88)91841-7","article-title":"Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis","volume":"1","author":"Plaitakis","year":"1988","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2169\/internalmedicine.38.401","article-title":"Branched-chain amino acid therapy for spinocerebellar degeneration: A pilot clinical crossover trial","volume":"38","author":"Mori","year":"1999","journal-title":"Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1007\/s12035-016-0078-x","article-title":"Omics to Explore Amyotrophic Lateral Sclerosis Evolution: The Central Role of Arginine and Proline Metabolism","volume":"54","author":"Patin","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1002\/mnfr.201400866","article-title":"Dietary phenolics against colorectal cancer\u2014From promising preclinical results to poor translation into clinical trials: Pitfalls and future needs","volume":"59","author":"Selma","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1600327","DOI":"10.1002\/mnfr.201600327","article-title":"Novel colon-available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro","volume":"61","author":"McDougall","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejphar.2016.12.008","article-title":"Terpenoids as anti-colon cancer agents\u2014A comprehensive review on its mechanistic perspectives","volume":"795","author":"Sharma","year":"2017","journal-title":"Eur. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1158\/1940-6207.CAPR-09-0247","article-title":"New role of (-)-epicatechin in enhancing the induction of growth inhibition and apoptosis in human lung cancer cells by curcumin","volume":"3","author":"Saha","year":"2010","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"ref_59","first-page":"44","article-title":"Synergistic effects of (--)-epigallocatechin gallate with (--)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9","volume":"59","author":"Suganuma","year":"1999","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1023\/A:1015290131096","article-title":"Dietary catechins and cancer incidence among postmenopausal women: The Iowa Women\u2019s Health Study (United States)","volume":"13","author":"Arts","year":"2002","journal-title":"Cancer Causes Control"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1158\/1055-9965.EPI-06-0785","article-title":"Dietary flavonoids and the risk of colorectal cancer","volume":"16","author":"Theodoratou","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1002\/elps.201200606","article-title":"Differences and similarities between LC-MS derived serum fingerprints of patients with B-cell malignancies","volume":"34","author":"Piszcz","year":"2013","journal-title":"Electrophoresis"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jpba.2014.12.026","article-title":"Urine metabolic fingerprinting using LC-MS and GC-MS reveals metabolite changes in prostate cancer: A pilot study","volume":"111","author":"Kordalewska","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2015.11.008","article-title":"Anthocyanins as inflammatory modulators and the role of the gut microbiota","volume":"33","author":"Morais","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3945\/ajcn.115.108555","article-title":"Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults","volume":"102","author":"Cassidy","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1007\/s10068-015-0246-1","article-title":"Anthocyanins in Rubus fruits and antioxidant and anti-inflammatory activities in RAW 264.7 cells","volume":"24","author":"Jung","year":"2015","journal-title":"Food Sci. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.toxlet.2015.09.020","article-title":"Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2\/Bach1 and NF-kappaB pathways","volume":"239","author":"Fratantonio","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.toxlet.2016.10.014","article-title":"Cyanidin-3-O-glucoside inhibits NF-kB signalling in intestinal epithelial cells exposed to TNF-alpha and exerts protective effects via Nrf2 pathway activation","volume":"264","author":"Ferrari","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuint.2016.05.004","article-title":"Phytochemicals and botanical extracts regulate NF-kappaB and Nrf2\/ARE reporter activities in DI TNC1 astrocytes","volume":"97","author":"Ajit","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Serra, D., Paixao, J., Nunes, C., Dinis, T.C., and Almeida, L.M. (2013). Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: Comparison with 5-aminosalicylic acid. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073001"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1021\/jf060253x","article-title":"Effect of cyanidin-3-O-glucoside on UVB-induced response in human keratinocytes","volume":"54","author":"Cimino","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1177\/0022034515604620","article-title":"Dual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells","volume":"94","author":"Park","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.foodchem.2017.12.015","article-title":"Molecular mechanism of action of Pelargonidin-3-O-glucoside, the main anthocyanin responsible for the anti-inflammatory effect of strawberry fruits","volume":"247","author":"Duarte","year":"2018","journal-title":"Food Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"230S","DOI":"10.1093\/ajcn\/81.1.230S","article-title":"Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies","volume":"81","author":"Manach","year":"2005","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/9\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:41Z","timestamp":1760177201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/9\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,26]]},"references-count":74,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["antiox9090789"],"URL":"https:\/\/doi.org\/10.3390\/antiox9090789","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2020,8,26]]}}}