{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:23:37Z","timestamp":1792157017794,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bahia State Research Foundation","award":["FAPESB\u2014Project N\u00ba 443\/2022"],"award-info":[{"award-number":["FAPESB\u2014Project N\u00ba 443\/2022"]}]},{"name":"Bahia State Research Foundation","award":["T.O. PET0002\/2022"],"award-info":[{"award-number":["T.O. PET0002\/2022"]}]},{"name":"Bahia State Research Foundation","award":["101\/2024"],"award-info":[{"award-number":["101\/2024"]}]},{"name":"Bahia State Research Foundation","award":["T.O. PET0007\/2024"],"award-info":[{"award-number":["T.O. 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PET0002\/2022"]}]},{"name":"National Council for Scientific and Technological Development","award":["101\/2024"],"award-info":[{"award-number":["101\/2024"]}]},{"name":"National Council for Scientific and Technological Development","award":["T.O. PET0007\/2024"],"award-info":[{"award-number":["T.O. PET0007\/2024"]}]},{"name":"National Council for Scientific and Technological Development","award":["Bol0151\/2022"],"award-info":[{"award-number":["Bol0151\/2022"]}]},{"name":"National Council for Scientific and Technological Development","award":["Bol0317\/2023"],"award-info":[{"award-number":["Bol0317\/2023"]}]},{"name":"National Council for Scientific and Technological Development","award":["03882\/2022\u20130"],"award-info":[{"award-number":["03882\/2022\u20130"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Amburana cearensis is a plant native to Brazil used in folk medicine for the treatment of several pathological conditions including stroke. Previous research indicates that a dichloromethane extract of A. cearensis seeds (EDAC), rich in coumarins, protects neural cells against oxygen and glucose deprivation (OGD) and glutamate-induced stress. However, further studies are needed to elucidate the role of coumarin, in the protective effect of EDAC. Glutamatergic excitotoxicity is an important cause of neuronal loss involved in the pathogenesis of Alzheimer\u2019s disease, Huntington\u2019s disease, Parkinson\u2019s disease, and ischemic stroke. Therefore, this study aimed to investigate the protective effects of coumarin isolated from EDAC against glutamate excitotoxicity in regulating MAPK pathway proteins and reactive oxygen species (ROS) production on PC12 cells. Furthermore, we aimed to investigate the protective effects of coumarin against cell death induced by OGD. We characterized the isolated compound from EDAC as coumarin by 1H and 13C-NMR. Thus, PC12 cells were exposed to OGD or glutamate (20 mM) and\/or treated with EDAC or coumarin (500 \u03bcg\/mL) for 24 h. Subsequently, cell viability was assessed by propidium iodide staining or by MTT test. Furthermore, the expression of MAPK pathway proteins was investigated by Western blot analysis and the expression of cleaved caspase-3 by immunofluorescence. Furthermore, reactive oxygen species (ROS) production was assessed by 2\u2032,7\u2032-dichlorofluorescein diacetate and CellROX. We observed that EDAC and coumarin were able to protect PC12 cells against OGD conditions. Moreover, EDAC totally inhibited the glutamate toxicity in PC12 cells. Meanwhile, coumarin mitigated the glutamate toxicity. Both were able to downregulate the expression of ERK1\/2 and phosphorylated ERK and inhibit caspase-3 activation. EDAC and coumarin also prevented the increase of ROS induced by treatment with H2O2 or glutamate. Our results evidenced that coumarin from A. cearensis is antioxidative and is an important cytoprotective compound in EDAC against glutamate excitotoxicity or OGD injury.<\/jats:p>","DOI":"10.3390\/antiox14040440","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T05:59:00Z","timestamp":1744091940000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dichloromethane Extract from Amburana cearensis (Allem\u00e3o) A.C. Sm. Seeds and Its Coumarin Reduce ROS Production and Protect PC12 Cells Against Glutamate Excitotoxicity and Oxygen-Glucose Deprivation"],"prefix":"10.3390","volume":"14","author":[{"given":"Fl\u00e1via Santos","family":"Sanches","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florisvaldo da Silva","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthia Cristina de O. S.","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-3030","authenticated-orcid":false,"given":"Ravena Pereira do","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Solano de Freitas","family":"Souza","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Bahia, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Salvador 41253-190, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-2893","authenticated-orcid":false,"given":"Maria de F\u00e1tima Dias","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3871","authenticated-orcid":false,"given":"Silvia Lima","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9622-5076","authenticated-orcid":false,"given":"Paulo R.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Metabolomics Research Group, Department of Organic Chemistry, Chemistry Institute, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-3807","authenticated-orcid":false,"given":"Rafael Short","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-9663","authenticated-orcid":false,"given":"Victor Diogenes Amaral da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador 40110-902, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12640-016-9600-1","article-title":"Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases","volume":"30","author":"Costa","year":"2016","journal-title":"Neurotox. 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