{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:58:53Z","timestamp":1774324733777,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"MINISTERIO DE ECONOM\u00cdA Y COMPETITIVIDAD OF SPAIN","doi-asserted-by":"publisher","award":["AG-2017-89342-P"],"award-info":[{"award-number":["AG-2017-89342-P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINISTERIO DE ECONOM\u00cdA Y COMPETITIVIDAD OF SPAIN","doi-asserted-by":"publisher","award":["CTS-259"],"award-info":[{"award-number":["CTS-259"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINISTERIO DE ECONOM\u00cdA Y COMPETITIVIDAD OF SPAIN","doi-asserted-by":"publisher","award":["FQM-182"],"award-info":[{"award-number":["FQM-182"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JUNTA DE ANDALUC\u00cdA","award":["AG-2017-89342-P"],"award-info":[{"award-number":["AG-2017-89342-P"]}]},{"name":"JUNTA DE ANDALUC\u00cdA","award":["CTS-259"],"award-info":[{"award-number":["CTS-259"]}]},{"name":"JUNTA DE ANDALUC\u00cdA","award":["FQM-182"],"award-info":[{"award-number":["FQM-182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 \u03bcg\/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2, IFN-\u03b3, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2\/HO-1 axis and the inhibition of JAK\/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ph15111338","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T09:01:42Z","timestamp":1667120502000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Roc\u00edo","family":"Mu\u00f1oz-Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"},{"name":"Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, HUVR, Junta de Andaluc\u00eda, CSIC, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-2404","authenticated-orcid":false,"given":"Marina","family":"S\u00e1nchez-Hidalgo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"},{"name":"Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, HUVR, Junta de Andaluc\u00eda, CSIC, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-8418","authenticated-orcid":false,"given":"Tatiana","family":"Montoya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"},{"name":"Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, HUVR, Junta de Andaluc\u00eda, CSIC, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-2720","authenticated-orcid":false,"given":"Manuel","family":"Alcarranza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"},{"name":"Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, HUVR, Junta de Andaluc\u00eda, CSIC, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3244-3781","authenticated-orcid":false,"given":"Juan","family":"Ortega-Vidal","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Organic Chemistry, Faculty of Experimental Sciences, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-8535","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Altarejos","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Organic Chemistry, Faculty of Experimental Sciences, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6625-3818","authenticated-orcid":false,"given":"Catalina","family":"Alarc\u00f3n-de-la-Lastra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"},{"name":"Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, HUVR, Junta de Andaluc\u00eda, CSIC, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/imm.12910","article-title":"Implications of Macrophage Polarization in Autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"ref_2","first-page":"57","article-title":"Innate Inflamation and Synovial Macrophages in osteoarthritis Pathophysiology","volume":"37","author":"Griffin","year":"2019","journal-title":"Clin. 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