{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:09:56Z","timestamp":1790255396499,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission through the National Recovery and Resilience Plan","award":["NPOO.C3.2.R3-I1.04.0257"],"award-info":[{"award-number":["NPOO.C3.2.R3-I1.04.0257"]}]},{"name":"European Commission through the National Recovery and Resilience Plan","award":["20282313"],"award-info":[{"award-number":["20282313"]}]},{"name":"Faculty of Science in Zagreb","award":["NPOO.C3.2.R3-I1.04.0257"],"award-info":[{"award-number":["NPOO.C3.2.R3-I1.04.0257"]}]},{"name":"Faculty of Science in Zagreb","award":["20282313"],"award-info":[{"award-number":["20282313"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer\u2019s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (A\u03b2) accumulation, tau pathology, and neuroinflammation in the Al\/D-galactose-induced rat model (Al\/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced A\u03b2 aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism.<\/jats:p>","DOI":"10.3390\/ijms26125743","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T10:47:22Z","timestamp":1750070842000},"page":"5743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Quercetin as a Therapeutic Option in a Rat Model of Aluminum Chloride- and D-Galactose-Induced Neurodegeneration"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-0673","authenticated-orcid":false,"given":"Marina","family":"Kukolj","sequence":"first","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-3606","authenticated-orcid":false,"given":"Nada","family":"Or\u0161oli\u0107","sequence":"additional","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Langer Horvat","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, \u0160alata 12, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-5931","authenticated-orcid":false,"given":"Barbara","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-4035","authenticated-orcid":false,"given":"Tatjana","family":"Ocrt","sequence":"additional","affiliation":[{"name":"Analytical Toxicilogy and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmen","family":"Branovi\u0107 \u010cakani\u0107","sequence":"additional","affiliation":[{"name":"Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-1993","authenticated-orcid":false,"given":"Romana","family":"Gra\u010dan","sequence":"additional","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Zrin\u0161\u010dak","sequence":"additional","affiliation":[{"name":"Ministry of the Interior, Vara\u017edin Regional Civil Protection Office, Kratka 1\/IV, 42000 Vara\u017edin, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-3919","authenticated-orcid":false,"given":"Maja","family":"Jazvin\u0161\u0107ak Jembrek","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Laboratory for Protein Dynamics, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Catholic University of Croatia, Ilica 244, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-9261","authenticated-orcid":false,"given":"Goran","family":"\u0160imi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, \u0160alata 12, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.clinbiochem.2019.04.015","article-title":"Clinical aspects of Alzheimer\u2019s disease","volume":"72","year":"2019","journal-title":"Clin. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1074\/mcp.R115.053330","article-title":"Neurodegeneration and Alzheimer\u2019s disease (AD). What Can Proteomics Tell Us About the Alzheimer\u2019s Brain?","volume":"15","author":"Perlson","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1111\/j.1471-4159.2006.03979.x","article-title":"The genetics of neurodegenerative diseases","volume":"97","author":"Hardy","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.15419\/bmrat.v6i11.575","article-title":"Chemicals used for the induction of Alzheimer\u2019s disease-like cognitive dysfunctions in rodents","volume":"6","author":"Mahdi","year":"2019","journal-title":"Biomed. Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26063","DOI":"10.1007\/s11356-021-18165-z","article-title":"Potential of flavonoids as anti-Alzheimer\u2019s agents: Bench to bedside","volume":"29","author":"Kaur","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tins.2022.11.006","article-title":"Entorhinal cortex dysfunction in Alzheimer\u2019s disease","volume":"46","author":"Igarashi","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Agarwal, M., Alam, M.R., Haider, M.K., Malik, M.Z., and Kim, D.K. (2020). Alzheimer\u2019s Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology. Nanomaterials, 11.","DOI":"10.3390\/nano11010059"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1016\/j.immuni.2022.10.016","article-title":"Emerging roles of innate and adaptive immunity in Alzheimer\u2019s disease","volume":"55","author":"Chen","year":"2022","journal-title":"Immunity"},{"key":"ref_9","first-page":"545","article-title":"Molecular toxicity of aluminium in relation to neurodegeneration","volume":"128","author":"Bharathi","year":"2008","journal-title":"Ind. J. Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1039\/c2mt00146b","article-title":"Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans","volume":"4","author":"Page","year":"2012","journal-title":"Metallomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.biopha.2018.04.152","article-title":"D-galactose and aluminium chloride induced rat model with cognitive impairments","volume":"103","author":"Chiroma","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s10072-018-3426-y","article-title":"Advances in dialysis encephalopathy research: A review","volume":"39","author":"Chen","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_13","unstructured":"Jackson, J.S., and Rout, P. (2020, January 07). Aluminum Toxicity, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK609094\/."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Or\u0161oli\u0107, N., and Jazvin\u0161\u0107ak Jembrek, M. (2022). Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810479"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuroscience.2016.02.055","article-title":"Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus","volume":"324","author":"Sharma","year":"2016","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2986796","DOI":"10.1155\/2016\/2986796","article-title":"Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More","volume":"2016","author":"Costa","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khan, A., Ali, T., Rehman, S.U., Khan, M.S., Alam, S.I., Ikram, M., Muhammad, T., Saeed, K., Badshah, H., and Kim, M.O. (2018). Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01383"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jadhav, R., and Kulkarni, Y.A. (2023). Neuroprotective Effect of Quercetin and Memantine against AlCl3-Induced Neurotoxicity in Albino Wistar Rats. Molecules, 28.","DOI":"10.3390\/molecules28010417"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1480553","DOI":"10.1155\/2022\/1480553","article-title":"Aluminum Poisoning with Emphasis on Its Mechanism and Treatment of Intoxication","volume":"2022","author":"Rahimzadeh","year":"2022","journal-title":"Emerg. Med. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-981-13-1370-7_3","article-title":"Entry and Deposit of Aluminum in the Brain","volume":"1091","author":"Wang","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100129","DOI":"10.1016\/j.crtox.2023.100129","article-title":"Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats","volume":"5","author":"Anyachor","year":"2023","journal-title":"Curr. Res. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101812","DOI":"10.1016\/j.toxrep.2024.101812","article-title":"Fisetin attenuates AlCl3-induced neurodegeneration by modulating oxidative stress and inflammatory cytokine release in adult albino wistar rats","volume":"13","author":"Anyanwu","year":"2024","journal-title":"Toxicol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/alz.12694","article-title":"Global estimates on the number of persons across the Alzheimer\u2019s disease continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimer Dement."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, X., Sun, X., Hou, N., Han, F., and Liu, Y. (2022). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132019. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.937486"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00204-023-03581-6","article-title":"The impact of aluminum exposure on human health","volume":"97","author":"Bonfiglio","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/j.jmb.2019.01.018","article-title":"Metal Toxicity Links to Alzheimer\u2019s Disease and Neuroinflammation","volume":"431","author":"Huat","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.biopha.2018.10.111","article-title":"Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches","volume":"109","author":"Chiroma","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2478\/intox-2014-0009","article-title":"Toxicity, mechanism and health effects of some heavy metals","volume":"7","author":"Jaishankar","year":"2014","journal-title":"Interdiscip. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1742-7843.2005.pto960205.x","article-title":"Disruption of neuronal calcium homeostasis after chronic aluminium toxicity in rats","volume":"96","author":"Kaur","year":"2005","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.taap.2007.02.001","article-title":"Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells","volume":"220","author":"Kim","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1177\/0960327112472993","article-title":"Quercetin vs chrysin: Effect on liver histopathology in diabetic mice","volume":"32","author":"Sirovina","year":"2013","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_32","first-page":"2817036","article-title":"Synergistic Effect of Quercetin and \u03b1-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats","volume":"16","author":"Arafah","year":"2018","journal-title":"J. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"NP11","DOI":"10.1177\/2156587215610032","article-title":"Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form (Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities","volume":"21","author":"Ademosun","year":"2016","journal-title":"J. Evid. Based Complement. Altern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-013-1659-x","article-title":"Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats","volume":"381","author":"Abdalla","year":"2013","journal-title":"Mol. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100149","DOI":"10.1016\/j.crphar.2022.100149","article-title":"Role of pro-inflammatory cytokines in Alzheimer\u2019s disease and neuroprotective effects of pegylated self-assembled nanoscaffolds","volume":"4","author":"Rani","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Alqarni, S.S., Afzal, M., Alharbi, K.S., Alenezi, S.K., Alsahli, T.G., Zaidi, S., Altyar, A.E., Ghaboura, N., Kazmi, I., and Mantargi, M.J.S. (2024). Rosiridin Protects Against Aluminum Chloride-Induced Memory Impairment via Modulation of BDNF\/NF\u03baB\/PI3K\/Akt Pathway in Rats. Medicina, 60.","DOI":"10.3390\/medicina60111812"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"He, C., Chen, B., Yang, H., and Zhou, X. (2025). The dual role of microglia in Alzheimer\u2019s disease: From immune regulation to pathological progression. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1554398"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jneuroim.2017.04.007","article-title":"Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology","volume":"309","author":"Hendrickx","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41392-024-02071-0","article-title":"Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Baj, J., Bargie\u0142, J., Cabaj, J., Skierkowski, B., Hunek, G., Portincasa, P., Flieger, J., and Smole\u0144, A. (2023). Trace Elements Levels in Major Depressive Disorder-Evaluation of Potential Threats and Possible Therapeutic Approaches. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015071"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s12011-018-1507-7","article-title":"Evaluation of Some Trace Elements and Vitamins in Major Depressive Disorder Patients: A Case-Control Study","volume":"189","author":"Yousif","year":"2019","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115171","DOI":"10.1016\/j.molliq.2020.115171","article-title":"Experimental and theoretical study on the coordination properties of quercetin towards aluminum(III), iron(III) and copper(II) in aqueous solution","volume":"325","author":"Corrente","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.jinorgbio.2010.04.010","article-title":"Aluminium interferes with hippocampal calcium signaling in a species-specific manner","volume":"104","author":"Nday","year":"2010","journal-title":"J. Inorg. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2147\/NDT.S350939","article-title":"Role of Calcium Homeostasis in Alzheimer\u2019s Disease","volume":"18","author":"Ge","year":"2022","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s10534-021-00298-w","article-title":"Effects of quercetin on the alterations of serum elements in chronic unpredictable mild stress-induced depressed rats","volume":"34","author":"Guan","year":"2021","journal-title":"Biometals"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xu, D., Hu, M.J., Wang, Y.Q., and Cui, Y.L. (2019). Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules, 24.","DOI":"10.3390\/molecules24061123"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/bcp.12621","article-title":"Emerging drug targets for A\u03b2 and tau in Alzheimer\u2019s disease: A systematic review","volume":"80","author":"West","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Colucci-D\u2019Amato, L., Speranza, L., and Volpicelli, F. (2020). Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207777"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijdevneu.2019.02.005","article-title":"Quercetin promotes learning and memory performance concomitantly with neural stem\/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus","volume":"74","author":"Karimipour","year":"2019","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_51","first-page":"143","article-title":"Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1 alpha pathway","volume":"33","author":"Liu","year":"2015","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chiang, M.C., Tsai, T.Y., and Wang, C.J. (2023). The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076328"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bmcl.2018.12.057","article-title":"Discovery of an isocoumarin analogue that modulates neuronal functions via neurotrophin receptor TrkB","volume":"29","author":"Sudarshan","year":"2019","journal-title":"Bioor. Med. Chem. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ejmech.2016.08.066","article-title":"Inhibition of the enzymes in the leukotriene and prostaglandin pathways in inflammation by 3-aryl isocoumarins","volume":"124","author":"Ramanan","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Odeh, D., Or\u0161oli\u0107, N., Adrovi\u0107, E., Biland\u017ei\u0107, N., Sedak, M., \u017darkovi\u0107, I., Lesar, N., and Balta, V. (2024). The Impact of the Combined Effect of Inhalation Anesthetics and Iron Dextran on Rats\u2019 Systemic Toxicity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126323"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Babi\u0107 Leko, M., Mihel\u010di\u0107, M., Jurasovi\u0107, J., Nikolac Perkovi\u0107, M., \u0160pani\u0107, E., Sekovani\u0107, A., Orct, T., Zub\u010di\u0107, K., Langer Horvat, L., and Plei\u0107, N. (2022). Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010467"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, W., Yang, Y., Fu, K., Zhang, D., and Wang, Z. (2022). Progress in ICP-MS Analysis of Minerals and Heavy Metals in Traditional Medicine. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.891273"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurment with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S0891-5849(02)00765-7","article-title":"Carbonyl modified proteins in cellular regulation, aging and disease","volume":"32","author":"Levine","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.exger.2006.10.006","article-title":"Protective effect of an extract of the oyster mushroom, Pleurotus ostreatus. On antioxidants of major organs of aged rats","volume":"42","author":"Jayakumar","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0003-2697(69)90064-5","article-title":"Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues","volume":"27","author":"Tietze","year":"1969","journal-title":"Anal. Biochem."},{"key":"ref_62","first-page":"70","article-title":"Superoxide dismutase assays","volume":"105","year":"1971","journal-title":"Meth. Enzymol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2990.1986.tb00677.x","article-title":"A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer\u2019s neurofibrillary tangles","volume":"12","author":"Yamamoto","year":"1986","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.902960102","article-title":"Unbiased stereological estimation of the number of neurons in the human hippocampus","volume":"296","author":"West","year":"1990","journal-title":"J. Comp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1523\/JNEUROSCI.3672-12.2013","article-title":"A transgenic alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric A\u03b2, and frank neuronal loss","volume":"33","author":"Cohen","year":"2013","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:27Z","timestamp":1760032347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125743"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125743","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}