{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:34:59Z","timestamp":1779204899431,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["P20-01171"],"award-info":[{"award-number":["P20-01171"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["2021\/CTS-259 by CTS-259"],"award-info":[{"award-number":["2021\/CTS-259 by CTS-259"]}]},{"name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidad, Junta de Andaluc\u00eda","award":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidad, Junta de Andaluc\u00eda","award":["P20-01171"],"award-info":[{"award-number":["P20-01171"]}]},{"name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidad, Junta de Andaluc\u00eda","award":["2021\/CTS-259 by CTS-259"],"award-info":[{"award-number":["2021\/CTS-259 by CTS-259"]}]},{"name":"FQM-102 and the Consejer\u00eda de Econom\u00eda, Conocimiento, Empresas y Universidad, Junta de Andaluc\u00eda","award":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-104767RB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"FQM-102 and the Consejer\u00eda de Econom\u00eda, Conocimiento, Empresas y Universidad, Junta de Andaluc\u00eda","award":["P20-01171"],"award-info":[{"award-number":["P20-01171"]}]},{"name":"FQM-102 and the Consejer\u00eda de Econom\u00eda, Conocimiento, Empresas y Universidad, Junta de Andaluc\u00eda","award":["2021\/CTS-259 by CTS-259"],"award-info":[{"award-number":["2021\/CTS-259 by CTS-259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The aim of this study was to explore the immunomodulatory effects of the natural enantiomer (R)-Sulforaphane (SFN) and the possible signaling pathways involved in an ex vivo model of LPS-stimulated murine peritoneal macrophages. Furthermore, we studied the epigenetic changes induced by (R)-SFN as well as the post-translational modifications of histone H3 (H3K9me3 and H3K18ac) in relation to the production of cytokines in murine splenocytes after LPS stimulation. (R)-SFN was able to modulate the inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages through the inhibition of reactive oxygen species (ROS), nitric oxide (NO) and cytokine (IL-1\u03b2, IL-6, IL-17, IL-18 and TNF-\u03b1) production by down-regulating the expression of pro-inflammatory enzymes (iNOS, COX-2 and mPGES-1). We also found that activation of the Nrf-2\/HO-1 axis and inhibition of the JAK2\/STAT-3, MAPK, canonical and non-canonical inflammasome signaling pathways could have been responsible for the immunomodulatory effects of (R)-SFN. Furthermore, (R)-SFN modulated epigenetic modifications through histone methylation (H3K9me3) and deacetylation (H3K18ac) in LPS-activated spleen cells. Collectively, our results suggest that (R)-SFN could be a promising epinutraceutical compound for the management of immunoinflammatory diseases.<\/jats:p>","DOI":"10.3390\/ph15080966","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T02:12:39Z","timestamp":1659665559000},"page":"966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Immunomodulatory Effects of (R)-Sulforaphane on LPS-Activated Murine Immune Cells: Molecular Signaling Pathways and Epigenetic Changes in Histone Markers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-2720","authenticated-orcid":false,"given":"Manuel","family":"Alcarranza","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-6740","authenticated-orcid":false,"given":"Isabel","family":"Villegas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Mu\u00f1oz-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Recio","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-387X","authenticated-orcid":false,"given":"Inmaculada","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, 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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1002\/ptr.7176","article-title":"Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials","volume":"35","author":"Mangla","year":"2021","journal-title":"Phytother. 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