{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:29Z","timestamp":1787027489261,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejer\u00eda de Salud. Junta de Andaluc\u00eda (Spain), Proyectos de Investigaci\u00f3n en Salud","award":["PI-0129-2017"],"award-info":[{"award-number":["PI-0129-2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg\/kg\/day p.o. HT, (4) DR treated with 0.5 mg\/kg\/day p.o. DHPG, (5) DR treated with 1 mg\/kg\/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.<\/jats:p>","DOI":"10.3390\/antiox10121983","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"1983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Synergistic Effect of 3\u2032,4\u2032-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus"],"prefix":"10.3390","volume":"10","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, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Facultad de Medicina, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Vallejo-Carmona","sequence":"additional","affiliation":[{"name":"Facultad de Enfermer\u00eda, Universidad Ana G. Mendez, Recinto Cupei, San Juan PR 00928, Puerto Rico"}],"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":"Esther","family":"Mart\u00edn-Aurioles","sequence":"additional","affiliation":[{"name":"Distrito Sanitario M\u00e1laga-Guadalhorce, UGC La Roca, 29009 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Rodriguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Facultad de Medicina, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ortega-Hombrados","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Facultad de Medicina, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Verdugo","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Facultad de Medicina, 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":"Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Instituto de la Grasa, 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":"Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Instituto de la Grasa, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-3760","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Gonz\u00e1lez-Correa","sequence":"additional","affiliation":[{"name":"Departmento de Farmacolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica (IBIMA), Facultad de Medicina, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.5334\/gh.853","article-title":"Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease: A cochrane review","volume":"15","author":"Rees","year":"2020","journal-title":"Glob. Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/joim.13333","article-title":"The Mediterranean diet and health: A comprehensive overview","volume":"290","author":"Willett","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2019.06.001","article-title":"Benefits of the Mediterranean diet: Epidemiological and molecular aspects","volume":"67","author":"Corella","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.3945\/jn.115.211557","article-title":"Olive oil polyphenols decrease LDL concentrations and LDL atherogenicity in men in a randomized controlled trial","volume":"145","author":"Remaley","year":"2015","journal-title":"J. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41430-018-0304-x","article-title":"Extra virgin olive oil: More than a healthy fat","volume":"72","year":"2019","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1017\/S0007114510000929","article-title":"Virgin olive oil administration improves the effect of aspirin on retinal vascular pattern in experimental diabetes mellitus","volume":"104","author":"Villalobos","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"786","DOI":"10.2174\/138161211795428885","article-title":"Extra virgin olive oil\u2019s polyphenols: Biological activities","volume":"17","author":"Visioli","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"D\u2019Angelo, C., Franceschelli, S., Quiles, J.L., and Speranza, L. (2020). Wide biological role of hydroxytyrosol: Possible therapeutic and preventive properties in cardiovascular diseases. Cells, 9.","DOI":"10.3390\/cells9091932"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"De La Cruz, J.P., P\u00e9rez de Algaba, I., Mart\u00edn-Aurioles, E., Arrebola, M.M., Ortega-Hombrados, L., Rodr\u00edguez-P\u00e9rez, M.D., Fern\u00e1ndez-Prior, M.\u00c1., Berm\u00fadez-Oria, A., Verdugo, C., and Gonz\u00e1lez-Correa, J.A. (2021). Extra virgin oil polyphenols improve the protective effects of hydroxytyrosol in an in vitro model of hypoxia-reoxygenation of rat brain. Brain Sci., 11.","DOI":"10.3390\/brainsci11091133"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6298","DOI":"10.1021\/jf803512r","article-title":"3,4-Dihydroxyphenylglycol (DHPG): An important phenolic compound present in natural table olives","volume":"57","author":"Lama","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00394-010-0162-3","article-title":"Anti-platelet effects of olive oil extract: In vitro functional and proteomic studies","volume":"50","author":"Zhang","year":"2011","journal-title":"Eur. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Prior, \u00c1., Berm\u00fadez-Oria, A., Mill\u00e1n-Linares, M.D.C., Fern\u00e1ndez-Bola\u00f1os, J., Espejo-Calvo, J.A., and Rodr\u00edguez-Guti\u00e9rrez, G. (2021). Anti-inflammatory and antioxidant activity of hydroxytyrosol and 3,4-dihydroxyphenyglycol purified from table olive effluents. Foods, 10.","DOI":"10.3390\/foods10020227"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s00394-014-0807-8","article-title":"Inhibitory and synergistic effects of natural olive phenols on human platelet aggregation and lipid peroxidation of microsomes from vitamin E-deficient rats","volume":"54","author":"Duthie","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pedan, V., Popp, M., Rohn, S., Nyfeler, M., and Bongartz, A. (2019). Characterization of phenolic compounds and their contribution to sensory properties of olive oil. Molecules, 24.","DOI":"10.3390\/molecules24112041"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4954","DOI":"10.1021\/jf0602267","article-title":"Comparison of the concentrations of phenolics compounds in olive oils and other plant oils: Correlation with antimicrobial activity","volume":"54","author":"Medina","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.1021\/acs.jafc.6b02945","article-title":"Neuroprotective effect of hydroxytyrosol in experimental diabetes mellitus","volume":"65","author":"Reyes","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jnutbio.2016.07.015","article-title":"Effects of hydroxytyrosol on cardiovascular biomarkers in experimental diabetes mellitus","volume":"37","author":"Reyes","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1021\/jf204223w","article-title":"New phenolic compounds hydrothermally extracted from the olive oil by-product alperujo and their antioxidative activities","volume":"60","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6804","DOI":"10.1021\/jf011712r","article-title":"Production in large quantities of highly purified hidroxitirosol from liquid-solid waste of two-phase olive oil processing or \u201cAlperujo\u201d","volume":"50","author":"Heredia","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/met.2014.0119","article-title":"Urine 8-isoprostane in relation to adiposity and insulin resistance in individuals at high cardiometabolic risk","volume":"13","author":"Costabile","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1800456","DOI":"10.1002\/mnfr.201800456","article-title":"Cardiovascular benefits of phenol-enriched virgin olive oils: New insights from the virgin olive oil and HDL functionality (VOHF) study","volume":"62","author":"Pedret","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ez, \u00c1., Jaramillo, S., Garc\u00eda-Borrego, A., Espejo-Calvo, J.A., Covas, M.I., Blanchart, G., de la Torre, R., Carrasco-Pancorbo, A., Mesa, M.D., and Fern\u00e1ndez-Prior, M.\u00c1. (2021). From green technology to functional olive oils: Assessing the best combination of olive tree-related extracts with complementary bioactivities. Antioxidants, 10.","DOI":"10.3390\/antiox10020202"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silva, A.F.R., Resende, D., Monteiro, M., Coimbra, M.A., Silva, A.M.S., and Cardoso, S.M. (2020). Application of hydroxytyrosol in the functional foods field: From ingredient to dietary supplements. Antioxidants, 9.","DOI":"10.3390\/antiox9121246"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Vlavcheski, F., Young, M., and Tsiani, E. (2019). Antidiabetic effects of hydroxytyrosol: In vitro and in vivo evidence. Antioxidants, 8.","DOI":"10.3390\/antiox8060188"},{"key":"ref_26","first-page":"1137","article-title":"Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable and have antioxidant properties in vitamin E-deficient rats--a proteomics and network analysis approach","volume":"56","author":"Duthie","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1021\/jf503357s","article-title":"Naturally occurring hydroxytyrosol derivatives: Hydroxytyrosyl acetate and 3,4-dihydroxyphenylglycol modulate inflammatory response in murine peritoneal macrophages. Potential utility as new dietary supplements","volume":"63","author":"Maya","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Silveira Rossi, J.L., Barbalho, S.M., Reverete de Araujo, R., Bechara, M.D., Sloan, K.P., and Sloan, L.A. (2021). Metabolic syndrome and cardiovascular diseases: Going beyon.; traditional risk factors. Diabetes Metab. Res. Rev., e3502.","DOI":"10.1002\/dmrr.3502"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MAJ.0b013e318224a147","article-title":"Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy","volume":"342","author":"Mitra","year":"2011","journal-title":"Am. J. Med. Sci."},{"key":"ref_30","first-page":"1157","article-title":"Virgin olive oil polyphenol hydroxytyrosol.; acetate inhibits in vitro platelet aggregation in human whole blood: Comparison with hydroxytyrosol and acetylsalicylic acid","volume":"101","author":"Asensi","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7872","DOI":"10.1021\/jf801502z","article-title":"Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on platelet function compared to acetylsalicylic acid","volume":"56","author":"Navas","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1253\/circj.CJ-08-1102","article-title":"Endothelial function and oxidative stress in cardiovascular diseases","volume":"73","author":"Higashi","year":"2009","journal-title":"Circ. J."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/12\/1983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:46:46Z","timestamp":1760168806000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/12\/1983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,13]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["antiox10121983"],"URL":"https:\/\/doi.org\/10.3390\/antiox10121983","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,13]]}}}