{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T09:17:05Z","timestamp":1765271825088,"version":"3.46.0"},"reference-count":76,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003069","name":"National Polytechnic Institute","doi-asserted-by":"publisher","award":["20201289","20200920"],"award-info":[{"award-number":["20201289","20200920"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke remains one of the leading causes of disability and mortality worldwide, and effective therapeutic options are still limited. Therefore, this study aimed to evaluate the neuroprotective effect of the aqueous extract of Bacopa procumbens (B. procumbens) in a murine model of ischemia\/reperfusion induced by middle cerebral artery occlusion (MCAO). This widely used model is generated by the transient intraluminal insertion of a nylon filament through the external carotid artery to occlude the middle cerebral artery, allowing controlled induction and subsequent reperfusion. Wistar rats underwent 2 h MCAO, followed by tail vein administration of B. procumbens extract (40 mg\/kg) or Edaravone (0.45 mg\/kg) before reperfusion. Neurological, histological, and molecular parameters were assessed 48 h later. Additionally, in silico analyses were performed to predict the antioxidant activity of the extract\u2019s major metabolites and to explore Nrf2-related signaling. B. procumbens treatment improved neurological condition, reduced the volume of the infarct lesion, increased the expression and activation of Akt and Nrf2, reduced lipid peroxidation (4-HNE), and downregulated AQP4, the main water channel involved in cerebral edema formation. These molecular effects were associated with enhanced neuronal survival and collectively resulted in significant neuroprotection in the MCAO model. In silico analysis identified key metabolites with high antioxidant potential through free radical scavenging, lipid peroxidation inhibition, and redox enzyme modulation. Nrf2-centered interactome analysis revealed eighty-two proteins linked to ischemia, neuroinflammation, neuronal death regulation, and oxidative stress response. These findings support the therapeutic potential of B. procumbens metabolites as neuroprotective agents against ischemic cerebral injury.<\/jats:p>","DOI":"10.3390\/ijms262411781","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T15:11:24Z","timestamp":1764947484000},"page":"11781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extract of Bacopa procumbens Mitigates Brain Injury and Improves Functional Outcomes Following Ischemia\u2013Reperfusion"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-0547","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Viveros-Bartolom\u00e9","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0282-9605","authenticated-orcid":false,"given":"Salvador","family":"P\u00e9rez-Mora","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"},{"name":"Research Department, Atria Scientific, Av. de los Maestros 452, Nueva Santa Mar\u00eda, Azcapotzalco, Mexico City 02800, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iv\u00e1n","family":"Alquisiras-Burgos","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebral Vascular Pathology, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez, Insurgentes Sur #3877, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ari Misael","family":"Mart\u00ednez-Torres","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maribel","family":"P\u00e9rez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-7216","authenticated-orcid":false,"given":"Juan","family":"Ocampo-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Histopathology, Academic Area of Veterinary Medicine, ICAp, Universidad Aut\u00f3noma del Estado de Hidalgo, Tulancingo de Bravo, Hidalgo 43600, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-5316","authenticated-orcid":false,"given":"Yazmin Montserrat","family":"Flores-Martinez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-7700","authenticated-orcid":false,"given":"Mar\u00eda del Consuelo","family":"G\u00f3mez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-1251","authenticated-orcid":false,"given":"Pen\u00e9lope","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebral Vascular Pathology, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez, Insurgentes Sur #3877, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-3717","authenticated-orcid":false,"given":"David Guillermo","family":"P\u00e9rez-Ishiwara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biomedicine I, Programa de Doctorado en Ciencias en Biotecnolog\u00eda y Maestr\u00eda en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","unstructured":"(2025, March 13). 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