{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:22:42Z","timestamp":1784128962750,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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":["20221123"],"award-info":[{"award-number":["20221123"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003069","name":"National Polytechnic Institute","doi-asserted-by":"publisher","award":["20254934"],"award-info":[{"award-number":["20254934"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron degeneration in the substantia nigra and striatum. Current treatments are largely palliative and frequently associated with adverse effects. This study aimed to evaluate the neuroprotective potential of an aqueous extract of Bacopa procumbens (B. procumbens) and the NAPEL formulation\u2014composed of five neuroactive compounds (Naringenin, Apigenin, Paeoniflorin, (\u2212)-Epicatechin, and Lupeol)\u2014in a murine model of MPTP-induced parkinsonism. Behavioral, histological, and molecular parameters were examined to elucidate underlying mechanisms of neuroprotection. Male mice received MPTP to induce parkinsonism, followed by oral administration of B. procumbens extract or NAPEL. Motor function was assessed through open-field-related parameters. Substantia nigra neuronal morphology was analyzed histologically. Molecular analyses focused on the Keap1\/Nrf2\/ARE pathway, HSF1, HIF-1\u03b1, antioxidant enzymes, and lipid peroxidation. Additionally, in silico analyses (GeneMANIA, STRING) were performed to explore regulatory networks associated with Nrf2, HSF1, and HIF-1\u03b1. The aqueous extract significantly improved motor performance, increased rearing events, enhanced central exploration, and increased total distance traveled. It preserved neuronal number and soma diameter in the substantia nigra. Molecularly, the extract activated the Keap1\/Nrf2\/ARE axis and induced HSF1 and HIF-1\u03b1, accompanied by increased SOD-1, CAT, and GSR expression and reduced lipid peroxidation. NAPEL also produced behavioral and histological improvements but did not activate Nrf2, HSF1, or HIF-1\u03b1 nor notably elevate antioxidant enzymes, except for CAT in the striatum. In silico analyses identified Nrf2, HSF1, and HIF-1\u03b1 as central nodes integrating oxidative stress, proteostasis, hypoxia, inflammation, and apoptotic responses. These findings support the neuroprotective potential of both B. procumbens aqueous extract and the NAPEL formulation, highlighting their value as promising therapeutic candidates for Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms262411914","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:32:17Z","timestamp":1765380737000},"page":"11914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aqueous Extract of Bacopa procumbens and the NAPEL Formulation Mitigate MPTP-Induced Neurotoxicity via Nrf2\/HSF1\/HIF-1\u03b1 Signaling in a Parkinson\u2019s Disease Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Maribel","family":"P\u00e9rez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0282-9605","authenticated-orcid":false,"given":"Salvador","family":"P\u00e9rez-Mora","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"},{"name":"Departamento de Investigaci\u00f3n, Atria Scientific, Av. de los Maestros 452, Nueva Santa Mar\u00eda, Azcapotzalco, Mexico City 02800, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-1502","authenticated-orcid":false,"given":"Marvin A.","family":"Soriano-Urs\u00faa","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofisiolog\u00eda, Escuela Superior de Medicina (ESM), Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Diaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-5316","authenticated-orcid":false,"given":"Yazmin Montserrat","family":"Flores-Martinez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-7216","authenticated-orcid":false,"given":"Juan","family":"Ocampo-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Histolog\u00eda e Histopatolog\u00eda, \u00c1rea Acad\u00e9mica de Medicina Veterinaria, Instituto de Ciencias Agropecuarias (ICAp), Universidad Aut\u00f3noma del Estado de Hidalgo, Tulancingo de Bravo, Hidalgo 43600, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Absalom","family":"Zamorano-Carrillo","sequence":"additional","affiliation":[{"name":"Laboratorio Biof\u00edsica Computacional, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-0547","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Viveros-Bartolom\u00e9","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-3717","authenticated-orcid":false,"given":"David Guillermo","family":"P\u00e9rez-Ishiwara","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular I, Escuela Nacional de Medicina y Homeopat\u00eda (ENMyH), Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"(2025, March 29). 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