{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:36:26Z","timestamp":1791513386274,"version":"4.3.4"},"reference-count":0,"publisher":"Juan Jos\u00e9 L\u00f3pez-Ibor Foundation","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Actas Esp Psiquiatr"],"abstract":"<jats:p>Background: Alzheimer's disease (AD) is a burdening disease and is the main cause of dementia. Quercetin (Que), an antioxidant, plays potential roles in treating age-related disorders, including AD. This study aimed to validate the effects of Que on AD and explore the underlying mechanisms.\u00a0\nMethods: Mice with no treatment, amyloid-\u03b2 A\u03b2 (1-42) treatment (for acquiring AD model), or A\u03b2 (1-42) plus Que treatment were used. Cognitive function was determined using the open field test (OFT), objective recognition test, and Y-maze test. In brain tissues, mRNA levels of inflammation cytokines, the M1 microglia marker cluster of differentiation (CD)86, and the M2 microglia markers arginase 1 (Arg1) and CD206 were measured. Nuclear factor E2-related factor 2 (NRF2)\/heme oxygenase-1 (HO1) pathway-related proteins were detected by western blot. Additionally, mechanisms were investigated using human microglia HMC3 cells treated with A\u03b2 (1-42) and A\u03b2 (1-42) plus Que. The NRF2\/HO1 pathway in HMC3 cells was inhibited using the selective inhibitor ML385. Cell viability and death were assessed using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release levels, respectively. Cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Levels of NRF2\/HO1 pathway-related proteins, inflammation cytokines, and oxidative stress-related markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (reduced glutathione (GSH)\/oxidized glutathione disulfide (GSSG)), were determined in HMC3 cells. Flow cytometry was used to determine M1 markers CD86 and CD80 and M2 markers CD206 and CD163.\u00a0\nResults: Cognitive ability was impaired in AD model mice, and Que treatment reversed this impairment (p &lt; 0.05). Levels of interleukin (IL)-1\u03b2, tumor necrosis factor-alpha (TNF-\u03b1), and IL-6 were increased, while M2 markers were decreased in the AD model mouse brain. Que treatment reversed these changes (p &lt; 0.001). The NRF2\/HO1 pathway was slightly inhibited in AD mice brain, while further activated by Que (p &lt; 0.05). Que reversed the A\u03b2 (1-42)-impaired cell viability. Through greatly activating NRF2\/HO1 pathway, Que suppressed A\u03b2 (1-42)-induced cell death, decreased A\u03b2 (1-42)-promoted IL-1\u03b2, TNF-\u03b1, IL-6, MDA, CD86 and CD80, increased A\u03b2 (1-42)-suppressed SOD and GSH\/GSSG, and greatly increased CD206 and CD163 (p &lt; 0.01).\u00a0\nConclusion: Quercetin, through the activation of the NRF2\/HO1 pathway, promotes M2 polarization of microglia, suppresses A\u03b2 (1-42)-induced inflammation and oxidative stress, protects microglia from A\u03b2 (1-42)-induced damage, improves cognitive function in mice, and demonstrates therapeutic potential for AD.<\/jats:p>","DOI":"10.62641\/aep.v52i6.1713","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T22:26:03Z","timestamp":1733437563000},"page":"786-799","source":"Crossref","is-referenced-by-count":24,"title":["Quercetin Regulates the Polarization of Microglia through the NRF2\/HO1 Pathway and Mitigates Alzheimer's Disease"],"prefix":"10.62641","volume":"52","author":[{"given":"Ying","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"48925","published-online":{"date-parts":[[2024,12,5]]},"container-title":["Actas Espa\u00f1olas de Psiquiatr\u00eda"],"original-title":[],"link":[{"URL":"https:\/\/actaspsiquiatria.es\/index.php\/actas\/article\/download\/1713\/2590","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/actaspsiquiatria.es\/index.php\/actas\/article\/download\/1713\/2590","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T22:26:03Z","timestamp":1733437563000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaspsiquiatria.es\/index.php\/actas\/article\/view\/1713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,12,5]]}},"URL":"https:\/\/doi.org\/10.62641\/aep.v52i6.1713","relation":{},"ISSN":["1578-2735","1139-9287"],"issn-type":[{"value":"1578-2735","type":"electronic"},{"value":"1139-9287","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12,5]]}}}