{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:43:34Z","timestamp":1784097814448,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010566","name":"Consejer\u00eda de Salud y Familias, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["PI-0129-2017"],"award-info":[{"award-number":["PI-0129-2017"]}],"id":[{"id":"10.13039\/501100010566","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PS17173. NUTRADAF,ITC-20161265"],"award-info":[{"award-number":["PS17173. NUTRADAF,ITC-20161265"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration\u2013effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 \u00b5M, while it increased its antioxidant effect at 50 and 100 \u00b5M and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT\u2019s antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone.<\/jats:p>","DOI":"10.3390\/brainsci11091133","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"1133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Extra Virgin Oil Polyphenols Improve the Protective Effects of Hydroxytyrosol in an In Vitro Model of Hypoxia-Reoxygenation of Rat Brain"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-6660","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"De La Cruz Cort\u00e9s","sequence":"first","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Facultad de Medicina, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-0165","authenticated-orcid":false,"given":"Inmaculada","family":"P\u00e9rez de Algaba","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Department, Hospital P\u00fablico de Montilla, 14550 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Mart\u00edn-Aurioles","sequence":"additional","affiliation":[{"name":"UGC La Roca, Distrito Sanitario M\u00e1laga-Guadalhorce, 29001 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-0718","authenticated-orcid":false,"given":"Mar\u00eda Monsalud","family":"Arrebola","sequence":"additional","affiliation":[{"name":"UGC Laboratorio Cl\u00ednico, Hospital de la Axarqu\u00eda, AGSEMA, 29740 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ortega-Hombrados","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Facultad de Medicina, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Rodr\u00edguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Facultad de Medicina, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-3081","authenticated-orcid":false,"given":"Mar\u00eda \u00c1frica","family":"Fern\u00e1ndez-Prior","sequence":"additional","affiliation":[{"name":"Instituto de la Grasa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Ctra. Utrera Km 1, Campus Universitario Pablo de Olavide, Edificio 46, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3632-3595","authenticated-orcid":false,"given":"Alejandra","family":"Berm\u00fadez-Oria","sequence":"additional","affiliation":[{"name":"Instituto de la Grasa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Ctra. Utrera Km 1, Campus Universitario Pablo de Olavide, Edificio 46, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Verdugo","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Facultad de Medicina, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Gonz\u00e1lez-Correa","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Facultad de Medicina, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pcad.2015.04.003","article-title":"Benefits of the Mediterranean diet: Insights from the PREDIMED Study","volume":"58","author":"Estruch","year":"2015","journal-title":"Prog. 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