{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:58:12Z","timestamp":1777640292525,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T00:00:00Z","timestamp":1625356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-028424"],"award-info":[{"award-number":["POCI-01-0145-FEDER-028424"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/79600\/2011"],"award-info":[{"award-number":["SFRH\/79600\/2011"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>The signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure\u2013activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at identifying the molecular mechanism underlying the anti-inflammatory properties of (S)-(+)-carvone. The murine macrophage cell line, Raw 264.7, was stimulated with bacterial lipopolysaccharide (LPS) to simulate inflammation. Western blot was used to assess protein levels and post-translational modifications. The subcellular localization of NF-\u03baB\/p65 was visualized by immunocytochemistry. An in vitro fluorometric assay was used to measure Sirtuin-1 (SIRT1) activity. (S)-(+)-carvone inhibited LPS-induced JNK1 phosphorylation, but not that of p38 and ERK1\/2 and also did not affect the phosphorylation and degradation of the NF-\u03baB inhibitor, I\u03baB-\u03b1. Accordingly, (S)-(+)-carvone did not affect LPS-induced phosphorylation of NF-\u03baB\/p65 on Ser536 and its nuclear translocation, but it significantly decreased LPS-induced I\u03baB-\u03b1 resynthesis, a NF-\u03baB-dependent process, and NF-\u03baB\/p65 acetylation on lysine (Lys) 310. Deacetylation of that Lys residue is dependent on the activity of SIRT1, which was found to be increased by (S)-(+)-carvone, while its protein levels were unaffected. Taken together, these results show that (S)-(+)-carvone is a new SIRT1 activator with the potential to counteract the chronic low-grade inflammation characteristic of age-related diseases.<\/jats:p>","DOI":"10.3390\/biomedicines9070777","type":"journal-article","created":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T22:34:36Z","timestamp":1625438076000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line"],"prefix":"10.3390","volume":"9","author":[{"given":"C\u00e1tia","family":"Sousa","sequence":"first","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, University of Coimbra, 3004\u2013504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-3124","authenticated-orcid":false,"given":"Bruno Miguel","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-9631","authenticated-orcid":false,"given":"Alcino Jorge","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, University of Coimbra, 3004\u2013504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-7132","authenticated-orcid":false,"given":"Alexandrina Ferreira","family":"Mendes","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, University of Coimbra, 3004\u2013504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2010.03.006","article-title":"Inflammation 2010: New adventures of an old flame","volume":"140","author":"Medzhitov","year":"2010","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.exger.2016.05.010","article-title":"Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype","volume":"82","author":"Malaquin","year":"2016","journal-title":"Exp. 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