{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:20Z","timestamp":1792806440870,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"japan society for the promotion of science","award":["18K09600 and 19K10151"],"award-info":[{"award-number":["18K09600 and 19K10151"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The immune response in periodontal lesions is involved in the progression of periodontal disease. Therefore, it is important to find a bioactive substance that has anti-inflammatory effects in periodontal lesions. This study aimed to examine if nobiletin, which is found in the peel of citrus fruits, could inhibit inflammatory responses in interleukin (IL)-1\u03b2-stimulated human periodontal ligament cells (HPDLCs). The release of cytokines (IL-6, IL-8, CXCL10, CCL20, and CCL2) and matrix metalloproteinases (MMP-1 and MMP-3) was assessed by ELISA. The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-\u03baB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis.\u00a0Our experiments revealed that nobiletin decreased the expression of inflammatory cytokines, cell adhesion molecules, and MMPs in IL-1\u03b2-stimulated HPDLCs. Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-\u03baB, MAPKs, and Akt pathways. These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1\u03b2-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-\u03baB, MAPKs, and Akt.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050667","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T22:36:24Z","timestamp":1620426984000},"page":"667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nobiletin Inhibits Inflammatory Reaction in Interleukin-1\u03b2-Stimulated Human Periodontal Ligament Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-4902","authenticated-orcid":false,"given":"Yoshitaka","family":"Hosokawa","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Oral Health Care Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1590\/1678-775720140259","article-title":"Host response mechanisms in periodontal diseases","volume":"23","author":"Silva","year":"2015","journal-title":"J. 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