{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:08:39Z","timestamp":1778746119837,"version":"3.51.4"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES)","doi-asserted-by":"publisher","award":["465637\/2014-0"],"award-info":[{"award-number":["465637\/2014-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016179","name":"National Institute of Science and Technology of Biodiversity and Natural Products-INCT-BioNat","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100016179","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016179","name":"National Institute of Science and Technology of Biodiversity and Natural Products-INCT-BioNat","doi-asserted-by":"publisher","award":["465637\/2014-0"],"award-info":[{"award-number":["465637\/2014-0"]}],"id":[{"id":"10.13039\/501100016179","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Medical Center of the Johannes Gutenberg University","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"University Medical Center of the Johannes Gutenberg University","award":["465637\/2014-0"],"award-info":[{"award-number":["465637\/2014-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as gua\u00e7atonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-\u03baB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue\u00ae assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-\u03baB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80\u2013100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases.<\/jats:p>","DOI":"10.3390\/antiox14080901","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-Inflammatory, Antioxidant, and Reparative Effects of Casearia sylvestris Leaf Derivatives on Periodontium In Vitro"],"prefix":"10.3390","volume":"14","author":[{"given":"Ang\u00e9lica L. R.","family":"Pavanelli","sequence":"first","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"},{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, S\u00e3o Paulo State University (UNESP), Araraquara 14801903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Eduarda S.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, S\u00e3o Paulo State University (UNESP), Araraquara 14801903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 T.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Drugs and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-909X","authenticated-orcid":false,"given":"Fl\u00e1vio A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Drugs and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Department of Drugs and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4920-2506","authenticated-orcid":false,"given":"Andr\u00e9 G.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Drugs and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-9290","authenticated-orcid":false,"given":"Joni A.","family":"Cirelli","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, S\u00e3o Paulo State University (UNESP), Araraquara 14801903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-1885","authenticated-orcid":false,"given":"James","family":"Deschner","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2756-5947","authenticated-orcid":false,"given":"Andressa V. B.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/oxfordjournals.jncimonographs.a003443","article-title":"Biology of oral mucosa and esophagus","volume":"29","author":"Squier","year":"2001","journal-title":"J. Natl. Cancer Inst. 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