{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:30:30Z","timestamp":1786707030263,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Commercialization Promotion Agency for R&D Outcomes","doi-asserted-by":"publisher","award":["RS-2025-02310153"],"award-info":[{"award-number":["RS-2025-02310153"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","award":["KGM1222612"],"award-info":[{"award-number":["KGM1222612"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KGM1222612"],"award-info":[{"award-number":["KGM1222612"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["RS-2024-00514237"],"award-info":[{"award-number":["RS-2024-00514237"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00514237"],"award-info":[{"award-number":["RS-2024-00514237"]}],"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Lipid mediators (LM), comprising 17S-hydroxy-docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50, were naturally generated from docosahexaenoic acid by soybean lipoxygenase and exhibit potent anti-inflammatory activities. However, their therapeutic potential in periodontitis (PD) remains unclear. Therefore, this study investigated the protective effects of LM against PD in vitro and in vivo. Methods: Human gingival fibroblasts (HGFs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS) to evaluate the anti-inflammatory effects of LM. Nitric oxide (NO) production, prostaglandin E2 (PGE2) level, inflammatory cytokines secretion, matrix metalloproteinase 9 (MMP9) expression, and NF-\u03baB\/STAT3 signaling pathways were analyzed. In vivo, a ligature-induced rat model of PD was established, and LM were orally administered at doses of 5, 10, and 20 \u03bcg\/kg once daily. The effects of LM were evaluated by histopathological examination, micro-computed tomography (micro-CT), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC). Results: In PG-LPS-stimulated HGFs, LM significantly reduced NO and PGE2 production by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, LM decreased the levels of interleukin (IL)-6, tumor necrosis factor-\u03b1 (TNF-\u03b1), IL-1\u03b2, and MMP9, accompanied by suppression of the NF-\u03baB and STAT3 signaling pathways. In the ligature-induced rat model of PD, LM significantly attenuated gingival inflammation and alveolar bone loss. Furthermore, IHC analysis revealed that LM markedly reduced the level of IL-6, TNF-\u03b1, MMP9, and phosphorylated STAT3 in gingival tissues. Conclusions: LM exerted protective effects against periodontitis by alleviating inflammatory response and reducing alveolar bone loss, which may be associated with suppression of the NF-\u03baB and STAT3 signaling pathways.<\/jats:p>","DOI":"10.3390\/nu18162659","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"2659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid Mediators Derived from Docosahexaenoic Acid Alleviate Periodontal Inflammation and Alveolar Bone Loss in Periodontitis Associated with Suppression of the NF-\u03baB and STAT3 Signaling Pathways"],"prefix":"10.3390","volume":"18","author":[{"given":"Yan","family":"Su","sequence":"first","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1550-0078","authenticated-orcid":false,"given":"Soon Kyu","family":"Kwon","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea"},{"name":"Department of Biotechnology, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hack Sun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjon","family":"Han","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-4224","authenticated-orcid":false,"given":"Yong-Suk","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Jeonbuk National University, Jeonju 54896, Republic of Korea"},{"name":"Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-628X","authenticated-orcid":false,"given":"Jung-Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Hyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-9981","authenticated-orcid":false,"given":"Jeong-Woo","family":"Seo","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e24216","DOI":"10.1016\/j.heliyon.2024.e24216","article-title":"A literature review of bioactive substances for the treatment of periodontitis: In vitro, in vivo and clinical studies","volume":"10","author":"Kim","year":"2024","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2485\/jhtb.23.255","article-title":"A new experimental mouse model of periodontitis using an orthodontic ligature wire","volume":"23","author":"Mizuno","year":"2014","journal-title":"J. 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