{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:30:30Z","timestamp":1785331830347,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2016M3A9B6903087"],"award-info":[{"award-number":["NRF-2016M3A9B6903087"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal diseases are caused by bacterial infection and may progress to chronic dental disease; severe inflammation may result in bone loss. Therefore, it is necessary to prevent bacterial infection or control inflammation. Periodontal ligament fibroblasts (PDLFs) are responsible for the maintenance of tissue integrity and immune and inflammatory events in periodontal diseases. The formation of bacterial complexes by Fusobacterium nucleatum and Porphyromonas gingivalis is crucial in the pathogenesis of periodontal disease. F. nucleatum is a facultative anaerobic species, considered to be a key mediator of dental plaque maturation and aggregation of other oral bacteria. P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting virulence factors. In this study, we investigated whether Osmunda japonica extract exerted anti-inflammatory effects in primary PDLFs stimulated by oral pathogens. PDLFs were stimulated with F. nucleatum or P. gingivalis. We showed that pro-inflammatory cytokine (IL-6 and IL-8) expression was induced by LPS or bacterial infection but decreased by treatment with O. japonica extract following bacterial infection. We found that the activation of NF-\u03baB, a transcription factor for pro-inflammatory cytokines, was modulated by O. japonica extract. Thus, O. japonica extract has immunomodulatory activity that can be harnessed to control inflammation.<\/jats:p>","DOI":"10.3390\/ijms21072453","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:57:14Z","timestamp":1585828634000},"page":"2453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Osmunda japonica Extract Suppresses Pro-Inflammatory Cytokines by Downregulating NF-\u03baB Activation in Periodontal Ligament Fibroblasts Infected with Oral Pathogenic Bacteria"],"prefix":"10.3390","volume":"21","author":[{"given":"Jihyoun","family":"Seong","sequence":"first","affiliation":[{"name":"Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-6490","authenticated-orcid":false,"given":"Jinkyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Kyong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weon-Jong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Jeju Biodiversity Research Institute (JBRI), Jeju Technopark (JTP), Jeju 63608, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunggon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong-Ki","family":"Kook","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea"},{"name":"Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"g2645","DOI":"10.1136\/bmj.g2645","article-title":"Time to take periodontitis seriously","volume":"348","author":"Chapple","year":"2014","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1902\/jop.2015.140520","article-title":"Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012","volume":"86","author":"Eke","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nri3785","article-title":"Periodontitis: From microbial immune subversion to systemic inflammation","volume":"15","author":"Hajishengallis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global Burden of Severe Periodontitis in 1990\u20132010","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","first-page":"1285","article-title":"Xylitol Inhibits Inflammatory Cytokine Expression Induced by Lipopolysaccharide from Porphyromonas gingivalis","volume":"12","author":"Han","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molmed.2014.11.004","article-title":"Polymicrobial synergy and dysbiosis in inflammatory disease","volume":"21","author":"Lamont","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41579-018-0089-x","article-title":"The oral microbiota: Dynamic communities and host interactions","volume":"16","author":"Lamont","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3389\/fcimb.2019.00429","article-title":"Persistent Exposure to Fusobacterium nucleatum Triggers Chemokine\/Cytokine Release and Inhibits the Proliferation and Osteogenic Differentiation Capabilities of Human Gingiva-Derived Mesenchymal Stem Cells","volume":"9","author":"Kang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hong, L., Sharp, T., Khorsand, B., Fischer, C., Eliason, S., Salem, A., Akkouch, A., Brogden, K., and Amendt, B.A. (2016). MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0169381"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1128\/iai.63.9.3576-3581.1995","article-title":"Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides","volume":"63","author":"Yamaji","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1600-0765.2006.00905.x","article-title":"Cytokine production in human periodontal ligament cells stimulated with Porphyromonas gingivalis","volume":"41","author":"Yamamoto","year":"2006","journal-title":"J. Periodontal Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1902\/jop.2012.110566","article-title":"Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: Comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray","volume":"83","author":"Colombo","year":"2012","journal-title":"J. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1034\/j.1600-0757.2002.03002.x","article-title":"Classifying periodontal diseases--a long-standing dilemma","volume":"30","author":"Armitage","year":"2002","journal-title":"Periodontol. 2000"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1902\/jop.2013.130142","article-title":"Antibiotic Resistance in Human Chronic Periodontitis Microbiota","volume":"85","author":"Rams","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_16","first-page":"27","article-title":"Herbal versus synthetic drugs; beliefs and facts","volume":"4","author":"Karimi","year":"2015","journal-title":"J. nephropharmacology"},{"key":"ref_17","first-page":"13","article-title":"Cisplatin therapy and the problem of gender-related nephrotoxicity","volume":"2","author":"Nasri","year":"2013","journal-title":"J. nephropharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1517\/14740338.3.6.615","article-title":"The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa)","volume":"3","author":"Huntley","year":"2004","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.3748\/wjg.15.3073","article-title":"A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity","volume":"15","author":"Nayebi","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1080\/14786419.2018.1501692","article-title":"Chemical constituents, cytotoxic and antioxidant activities of extract from the rhizomes of Osmunda japonica Thunb","volume":"34","author":"Bowen","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s11655-013-1460-4","article-title":"Divergent immunomodulatory effects of extracts and phenolic compounds from the fern Osmunda japonica Thunb","volume":"19","author":"Zhu","year":"2013","journal-title":"Chin. J. Integr. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1007\/BF00980686","article-title":"Responses of maxillary sensilla styloconica inBombyx mori to glucosides fromOsmunda japonica, a nonhost plant","volume":"19","author":"Shimizu","year":"1993","journal-title":"J. Chem. Ecol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yun, I.-G., Ahn, S.H., Yoon, W.-J., Kim, C.S., Lim, Y.K., Kook, J.-K., Jung, S., Choi, C.-H., and Lee, T.-H. (2018). Litsea japonica Leaf Extract Suppresses Proinflammatory Cytokine Production in Periodontal Ligament Fibroblasts Stimulated with Oral Pathogenic Bacteria or Interleukin-1\u03b2. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092494"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/jre.12248","article-title":"Bacterial invasion and persistence: Critical events in the pathogenesis of periodontitis?","volume":"50","author":"Ji","year":"2014","journal-title":"J. Periodontal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000329670","article-title":"Innate cellular responses to the periodontal biofilm","volume":"15","author":"Benakanakere","year":"2012","journal-title":"Front. Oral Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1111\/jcpe.12937","article-title":"Dental plaque-induced gingival conditions","volume":"45","author":"Murakami","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00203-016-1223-7","article-title":"NOX1\/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis","volume":"198","author":"Ahn","year":"2016","journal-title":"Arch. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S200","DOI":"10.1093\/clinids\/16.Supplement_4.S200","article-title":"Stimulation of B Lymphocytes by Lipopolysaccharides from Anaerobic Bacteria","volume":"16","author":"Hofstad","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1600-051X.1998.tb02414.x","article-title":"Microbiota of health, gingivitis, and initial periodontitis","volume":"25","author":"Tanner","year":"1998","journal-title":"J. Clin. Periodontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1034\/j.1600-051x.2000.027009648.x","article-title":"Comparison of the microbiota of supra- and subgingival plaque in health and periodontitis","volume":"27","author":"Haffajee","year":"2000","journal-title":"J. Clin. Periodontol."},{"key":"ref_31","first-page":"7","article-title":"Evidence of bacterial etiology: A historical perspective","volume":"1994","author":"Socransky","year":"2000","journal-title":"Periodontology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1086\/341778","article-title":"Inflammation and Tissue Loss Caused by Periodontal Pathogens Is Reduced by Interleukin-1 Antagonists","volume":"186","author":"DeLima","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/omi.12167","article-title":"Caveolin-1 serves as a negative effector in senescent human gingival fibroblasts duringFusobacterium nucleatuminfection","volume":"32","author":"Ahn","year":"2016","journal-title":"Mol. Oral Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1128\/IAI.66.4.1660-1665.1998","article-title":"Local Chemokine Paralysis, a Novel Pathogenic Mechanism for Porphyromonas gingivalis","volume":"66","author":"Darveau","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/jre.12410","article-title":"Immunologic characteristics of human gingival fibroblasts in response to oral bacteria","volume":"52","author":"Jang","year":"2016","journal-title":"J. Periodontal Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cell.2017.07.008","article-title":"Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy","volume":"170","author":"Yu","year":"2017","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jia, Y.P., Wang, K., Zhang, Z.J., Tong, Y.N., Han, D., Hu, C.Y., Li, Q., Xiang, Y., Mao, X.-H., and Tang, B. (2017). TLR2\/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186179"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lu, W., Gu, J.-Y., Zhang, Y.-Y., Gong, D.-J., Zhu, Y.-M., and Sun, Y. (2018). Tolerance induced by Porphyromonas gingivalis may occur independently of TLR2 and TLR4. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200946"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.4103\/1673-5374.251290","article-title":"Toll-like receptor 4 and protease-activated receptor 2 in physiology and pathophysiology of the nervous system: More than just receptor cooperation?","volume":"14","author":"Widera","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1177\/00220345880670011301","article-title":"A Comparative Study of Human Periodontal Ligament Cells and Gingival Fibroblasts in vitro","volume":"67","author":"Somerman","year":"1988","journal-title":"J. Dent. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2453\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:14:24Z","timestamp":1760174064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["ijms21072453"],"URL":"https:\/\/doi.org\/10.3390\/ijms21072453","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}