{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:37:08Z","timestamp":1789987028564,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DOD","award":["GW180044"],"award-info":[{"award-number":["GW180044"]}]},{"name":"DOD","award":["VA I01BX3230"],"award-info":[{"award-number":["VA I01BX3230"]}]},{"name":"DOD","award":["I01BX5894"],"award-info":[{"award-number":["I01BX5894"]}]},{"name":"DOD","award":["IPN 20195988"],"award-info":[{"award-number":["IPN 20195988"]}]},{"name":"DOD","award":["CONACYT 283938"],"award-info":[{"award-number":["CONACYT 283938"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: We previously reported that the flavanol (+)-epicatechin (+Epi) enhances adult mice short-term working memory and neurogenesis. This study aimed to characterize the effects of +Epi on short- and long-term memory, to modulate mitochondria structure\/function, oxidative stress (OS) and inflammation associated cytokines in the hippocampus and pre-frontal cortex of aged rats. Methods: Experiments were conducted using aged (23 month old) male Sprague Dawley rats. The control group (n = 6\/group) were exposed to vehicle (water) only while the treated group, was provided +Epi at 1 mg\/kg\/day by oral gavage for 8 weeks. Open-field recognition tests were used to evaluate short- and long-term memory. The hippocampus and frontal cortex were sampled and citrate synthase activity, ATP levels, mitochondrial proteins, cytokines (IL-1\u03b2, IL-6, TNF-a and IL-11), protein carbonylation, lipid peroxidation (malonaldehyde; MDA), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase activity were quantified. Results: There was a significant improvement in both short- and long-term memory in the +Epi treated group vs. controls. Mitochondrial bioenergetics also improved with treatment as determined by increased citrate synthase activity and ATP content. Relative levels of the mitochondrial proteins mitofilin and complex V increased with +Epi. +Epi suppressed protein carbonyls and MDA levels. OS buffering systems were significantly enhanced with +Epi as per increases in SOD2, GPx and catalase enzyme activities. +Epi also decreased pro-inflammatory and stimulated anti-inflammatory cytokines vs. controls. Conclusions: Results demonstrate +Epi improves mitochondrial function, reduces OS and inflammation in the hippocampus and cortex leading to improved short- and long-term memory in aged animals providing evidence for possible mechanisms of action.<\/jats:p>","DOI":"10.3390\/nu17223611","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:03:15Z","timestamp":1763564595000},"page":"3611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stimulatory Effects of (+)-Epicatechin on Short- and Long-Term Memory in Aged Rats: Underlying Mechanisms"],"prefix":"10.3390","volume":"17","author":[{"given":"Israel","family":"Ramirez-Sanchez","sequence":"first","affiliation":[{"name":"Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, IPN, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Salas-Gutierrez","sequence":"additional","affiliation":[{"name":"Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, IPN, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-9175","authenticated-orcid":false,"given":"Rosa","family":"Ordo\u00f1ez-Razo","sequence":"additional","affiliation":[{"name":"Unidad de Investigacion Medica en Genetica Humana, Hospital de Pediatria, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-4093","authenticated-orcid":false,"given":"Pilar","family":"Ortiz-Vilchis","sequence":"additional","affiliation":[{"name":"Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, IPN, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-8566","authenticated-orcid":false,"given":"Claudia","family":"Calzada-Mendoza","sequence":"additional","affiliation":[{"name":"Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, IPN, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Najera","sequence":"additional","affiliation":[{"name":"School of Medicine, UCSD, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Mendoza-Lorenzo","sequence":"additional","affiliation":[{"name":"Division Academica de Ciencias Basicas, Universidad Juarez Autonoma de Tabasco, Villahermosa 86660, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-3934","authenticated-orcid":false,"given":"Guillermo","family":"Ceballos","sequence":"additional","affiliation":[{"name":"Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, IPN, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Villarreal","sequence":"additional","affiliation":[{"name":"School of Medicine, UCSD, La Jolla, CA 92093, USA"},{"name":"VA San Diego Health Care, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bmb\/ldp033","article-title":"Age-associated cognitive decline","volume":"92","author":"Deary","year":"2009","journal-title":"Br. 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