{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:18Z","timestamp":1792789638785,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IN217822"],"award-info":[{"award-number":["IN217822"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IN222925"],"award-info":[{"award-number":["IN222925"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IN216922"],"award-info":[{"award-number":["IN216922"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["225425"],"award-info":[{"award-number":["225425"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"crossref"}]},{"award":["IN217822"],"award-info":[{"award-number":["IN217822"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["IN222925"],"award-info":[{"award-number":["IN222925"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["IN216922"],"award-info":[{"award-number":["IN216922"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["225425"],"award-info":[{"award-number":["225425"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"publisher","award":["CBF2023-2024-878"],"award-info":[{"award-number":["CBF2023-2024-878"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"publisher","award":["IFC 2016-2282"],"award-info":[{"award-number":["IFC 2016-2282"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CBF2023-2024-878"],"award-info":[{"award-number":["CBF2023-2024-878"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"award":["IFC 2016-2282"],"award-info":[{"award-number":["IFC 2016-2282"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The remarkable increase in human life expectancy has been accompanied by a rising global incidence of neurodegenerative disorders, particularly Alzheimer\u2019s disease. This condition is characterized by progressive accumulation of soluble and insoluble amyloid-beta peptides, neuroinflammation, and synaptic dysfunction in the hippocampus, leading to impaired higher-order cognition. Epidemiological evidence indicates that women are disproportionately affected; however, female-specific pathology remains understudied. Here, we evaluated the therapeutic potential of a hydroalcoholic extract of Malva parviflora in female 5XFAD mice following prolonged intragastric administration initiated after disease establishment. Long-term treatment shifted cognitive performance toward a phenotype comparable to wild-type littermates, an improvement associated with reduced soluble amyloid-beta levels in the hippocampus and peripheral circulation, and significant attenuation of reactive astrogliosis as evidenced by reduced hippocampal glial fibrillary acidic protein levels. Because reactive astrocytes impair synaptic activity and metabolic homeostasis during disease progression, we examined the direct effects of Malva parviflora on synaptic plasticity ex vivo. Incubation of hippocampal synaptosomes from adult female 5XFAD mice with the extract restored chemically induced long-term potentiation. These findings demonstrate that Malva parviflora attenuates key pathological hallmarks of Alzheimer\u2019s disease and promotes cognitive recovery, supporting its potential as a plant-derived therapeutic candidate, particularly in females most affected by Alzheimer\u2019s disease. Future studies including both sexes under a therapeutic paradigm are needed to determine the generalizability of these findings.<\/jats:p>","DOI":"10.3390\/ijms27198665","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Administration of Malva parviflora Hydroalcoholic Extract Restores Cognitive Function Consistent with a Resilient Phenotype in Female 5XFAD"],"prefix":"10.3390","volume":"27","author":[{"given":"Itzel","family":"Rojas-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eladio","family":"Cortes-Flores","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nohemi","family":"Camacho-Concha","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3504-7966","authenticated-orcid":false,"given":"Jorge Luis","family":"Almaz\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Ram\u00edrez-Lugo","sequence":"additional","affiliation":[{"name":"Departamento de Neurociencia Cognitiva, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, AP 70-253, Ciudad de M\u00e9xico 04510, Ciudad de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1963-5935","authenticated-orcid":false,"given":"Esther","family":"Crivelli-Galindo","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina E.","family":"Ramirez-Serrano","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-1218","authenticated-orcid":false,"given":"Gustavo","family":"Pedraza-Alva","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-1653","authenticated-orcid":false,"given":"Leonor","family":"P\u00e9rez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","first-page":"2619","article-title":"Sex Differences in the Progression to Alzheimer\u2019s Disease: A Combination of Functional and Structural Markers","volume":"46","author":"Cuesta","year":"2024","journal-title":"GeroScience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature11729","article-title":"NLRP3 Is Activated in Alzheimer\u2019s Disease and 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