{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:41:41Z","timestamp":1790343701064,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Foundation \u00abMutua Madrile\u00f1a\u00bb (Fourth edition of Grants for Medical Research Projects)","award":["AGL2008-04892-C03-02"],"award-info":[{"award-number":["AGL2008-04892-C03-02"]}]},{"name":"Medical Research Foundation \u00abMutua Madrile\u00f1a\u00bb (Fourth edition of Grants for Medical Research Projects)","award":["CTQ2010-16170"],"award-info":[{"award-number":["CTQ2010-16170"]}]},{"name":"Spanish Ministry of Education and Science","award":["AGL2008-04892-C03-02"],"award-info":[{"award-number":["AGL2008-04892-C03-02"]}]},{"name":"Spanish Ministry of Education and Science","award":["CTQ2010-16170"],"award-info":[{"award-number":["CTQ2010-16170"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["AGL2008-04892-C03-02"],"award-info":[{"award-number":["AGL2008-04892-C03-02"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["CTQ2010-16170"],"award-info":[{"award-number":["CTQ2010-16170"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Quercetin has been studied extensively for its anti-Alzheimer\u2019s disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and rutin on intracellular redox homeostasis of the brain (reduced glutathione\/oxidized glutathione, GSH\/GSSG), its correlation with \u03b2-site APP cleaving enzyme 1 (BACE1) activity, and amyloid precursor protein (APP) expression in transgenic TgAPP mice (bearing human Swedish mutation APP transgene, APPswe). On the basis that BACE1 protein and APP processing are regulated by the ubiquitin\u2013proteasome pathway and that supplementation with GSH protects neurons from proteasome inhibition, we investigated whether a diet containing quercetin or rutin (30 mg\/kg\/day, 4 weeks) diminishes several early signs of AD. Genotyping analyses of animals were carried out by PCR. In order to determine intracellular redox homeostasis, spectrofluorometric methods were adopted to quantify GSH and GSSG levels using o-phthalaldehyde and the GSH\/GSSG ratio was ascertained. Levels of TBARS were determined as a marker of lipid peroxidation. Enzyme activities of SOD, CAT, GR, and GPx were determined in the cortex and hippocampus. \u0392ACE1 activity was measured by a secretase-specific substrate conjugated to two reporter molecules (EDANS and DABCYL). Gene expression of the main antioxidant enzymes: APP, BACE1, a Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), caspase-3, caspase-6, and inflammatory cytokines were determined by RT-PCR. First, overexpression of APPswe in TgAPP mice decreased GSH\/GSSG ratio, increased malonaldehyde (MDA) levels, and, overall, decreased the main antioxidant enzyme activities in comparison to wild-type (WT) mice. Treatment of TgAPP mice with quercetin or rutin increased GSH\/GSSG, diminished MDA levels, and favored the enzyme antioxidant capacity, particularly with rutin. Secondly, both APP expression and BACE1 activity were diminished with quercetin or rutin in TgAPP mice. Regarding ADAM10, it tended to increase in TgAPP mice with rutin treatment. As for caspase-3 expression, TgAPP displayed an increase which was the opposite with rutin. Finally, the increase in expression of the inflammatory markers IL-1\u03b2 and IFN-\u03b3 in TgAPP mice was lowered by both quercetin and rutin. Collectively, these findings suggest that, of the two flavonoids, rutin may be included in a day-to-day diet as a form of adjuvant therapy in AD.<\/jats:p>","DOI":"10.3390\/ijms24054863","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:27:25Z","timestamp":1677810445000},"page":"4863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Paloma","family":"Bermejo-Besc\u00f3s","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-8358","authenticated-orcid":false,"given":"Karim L.","family":"Jim\u00e9nez-Aliaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juana","family":"Bened\u00ed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-2726","authenticated-orcid":false,"given":"Sagrario","family":"Mart\u00edn-Arag\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1315","DOI":"10.1212\/WNL.0000000000200035","article-title":"Association of CSF, Plasma, and Imaging Markers of Neurodegeneration with Clinical Progression in People with Subjective Cognitive Decline","volume":"98","author":"Ebenau","year":"2022","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dominguez, L.J., Veronese, N., Vernuccio, L., Catanese, G., Inzerillo, F., Salemi, G., and Barbagallo, M. 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