{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:13:01Z","timestamp":1791252781805,"version":"4.1.0"},"reference-count":177,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-\u03b2 (A\u03b2) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation\u2014driven by microglial activation and pro-inflammatory cytokine release\u2014as a key contributor to AD pathogenesis and progression. In the absence of effective disease-modifying therapies, attention has turned to natural compounds with multi-target potential. Flavonoids, a diverse class of plant-derived polyphenols, have demonstrated neuroprotective properties through antioxidant activity, modulation of neuroinflammatory pathways, and interference with both A\u03b2 aggregation and tau pathology. This narrative review provides an integrative overview of current findings on the mechanisms of action of key flavonoids\u2014such as quercetin, luteolin, and apigenin\u2014in both preclinical and clinical models. Emphasis is placed on their effects on microglial polarization, oxidative stress reduction, mitochondrial support, and synaptic function enhancement. Moreover, flavonoids show synergistic potential when combined with standard pharmacotherapies, such as acetylcholinesterase inhibitors, and may offer broader cognitive benefits in patients with mild cognitive impairment (MCI). Despite these promising findings, significant challenges persist, including poor bioavailability, inter-individual variability, and limited long-term clinical data. This review identifies critical gaps in knowledge and outlines future directions, including targeted drug delivery systems, biomarker-guided personalization, and long-duration trials. Flavonoids thus emerge not only as promising neuroprotective agents but also as complementary candidates in the development of future multi-modal strategies for AD treatment.<\/jats:p>","DOI":"10.3390\/brainsci15050485","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T03:05:15Z","timestamp":1746414315000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Role of Selected Flavonoids in Modulating Neuroinflammation in Alzheimer\u2019s Disease: Mechanisms and Therapeutic Potential"],"prefix":"10.3390","volume":"15","author":[{"given":"Joanna","family":"Kruszka","sequence":"first","affiliation":[{"name":"Student Research Club of Medical Biology and Biochemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Marty\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-3882","authenticated-orcid":false,"given":"Karolina","family":"Szewczyk-Golec","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-4796","authenticated-orcid":false,"given":"Alina","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-5065","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Nuszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.31887\/DCNS.2003.5.1\/hhippius","article-title":"The Discovery of Alzheimer\u2019s Disease","volume":"5","author":"Hippius","year":"2003","journal-title":"Dialogues Clin. 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