{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:30:28Z","timestamp":1784071828041,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015826","name":"The Korean Society of Ginseng","doi-asserted-by":"publisher","award":["This work was supported by 2019 grant from the Korean Society of Ginseng"],"award-info":[{"award-number":["This work was supported by 2019 grant from the Korean Society of Ginseng"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Periodontitis is an infectious inflammatory disease of tissues around teeth that destroys connective tissues and is characterized by the loss of periodontal ligaments and alveolar bone. A new treatment strategy is needed owing to the limitations of the current surgical treatment method and the side effects of anti-inflammatory drugs. Therefore, here, we assessed whether Panax ginseng fruit extract (PGFE) is a new therapeutic agent for periodontitis in vitro and in vivo. According to the results, PGFE suppressed pro-inflammatory cytokines such as tumor necrosis factor-\u03b1, interleukin (IL)-1\u03b2, and IL-6, and pro-inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase-2 through heme oxygenase-1 expression in human periodontal ligament cells stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS). In addition, the osteogenic induction of human periodontal ligament cells was inhibited by PG-LPS, and protein and mRNA levels of osteogenic markers such as alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2) were increased. The efficacy of PGFE for inhibiting periodontitis in vitro was demonstrated in a representative in vitro model of periodontitis induced by ligature and PG-LPS. Subsequently, hematoxylin and eosin staining and micro-computed tomography of the euthanized experimental animal model confirmed suppressed periodontal inflammation, which is an important strategy for treating periodontitis and for recovering the resulting alveolar bone loss. Therefore, PGFE is a potential, novel therapeutic agent for periodontal diseases.<\/jats:p>","DOI":"10.3390\/antiox9121221","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T11:15:43Z","timestamp":1606994143000},"page":"1221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Panax ginseng Fruit Has Anti-Inflammatory Effect and Induces Osteogenic Differentiation by Regulating Nrf2\/HO-1 Signaling Pathway in In Vitro and In Vivo Models of Periodontitis"],"prefix":"10.3390","volume":"9","author":[{"given":"Eun-Nam","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177, Dalgubeol-daero, Jung-gu, Daegu 41940, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8006-6402","authenticated-orcid":false,"given":"Eui Kyun","family":"Park","sequence":"additional","affiliation":[{"name":"Departments of Oral Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu 41940, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-5683","authenticated-orcid":false,"given":"Jae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177, Dalgubeol-daero, Jung-gu, Daegu 41940, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil-Saeng","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mehy.2017.06.022","article-title":"Is periodontitis a risk factor for infections in cirrhotic patients","volume":"106","author":"Profio","year":"2017","journal-title":"Med. Hypotheses"},{"key":"ref_2","first-page":"1041","article-title":"Current view of risk factors for periodontal diseases","volume":"67","author":"Genco","year":"1996","journal-title":"J. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0898-6568(00)00149-2","article-title":"LPS induction of gene expression in human monocytes","volume":"13","author":"Guha","year":"2001","journal-title":"Cell. Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1902\/jop.1993.64.11.1013","article-title":"Marginal Periodontitis and Cytokines: A Review of the Literature","volume":"64","author":"Kjeldsen","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.archoralbio.2010.08.015","article-title":"Supplementation of green tea catechins in dentifrices suppresses gingival oxidative stress and periodontal inflammation","volume":"56","author":"Maruyama","year":"2011","journal-title":"Arch. Oral Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1631\/jzus.B0920279","article-title":"Interleukin-6 polymorphisms modify the risk of periodontitis: A systematic review and meta-analysis","volume":"10","author":"Shao","year":"2009","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bone.2006.07.003","article-title":"Dexamethasone\u2019s enhancement of osteoblastic markers in human periodontal ligament cells is associated with inhibition of collagenase expression","volume":"40","author":"Hayami","year":"2007","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s11626-014-9748-z","article-title":"Various methods for isolation of multipotent human periodontal ligament cells for regenerative medicine","volume":"50","author":"Bao","year":"2014","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_10","first-page":"ZE07","article-title":"Epigenetics and Periodontitis: A Contemporary Review","volume":"10","author":"Ari","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1902\/jop.2000.71.6.1009","article-title":"Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats","volume":"71","author":"Bezerra","year":"2000","journal-title":"J. Periodontol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1152\/ajplung.2000.279.6.L1029","article-title":"Heme oxygenase: Colors of defense against cellular stress","volume":"279","author":"Otterbein","year":"2000","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2015.05.036","article-title":"Oxidative stress response and Nrf2 signaling in aging","volume":"88","author":"Zhang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"636","DOI":"10.5483\/BMBRep.2015.48.11.112","article-title":"N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2\/HO-1 pathway","volume":"48","author":"Lee","year":"2015","journal-title":"BMB Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1021\/acs.jafc.5b05157","article-title":"Glabridin alleviates the toxic effects of Methylglyoxal on osteoblastic MC3T3-E1 cells by increasing expression of the glyoxalase system and Nrf2\/HO-1 signaling and protecting mitochondrial function","volume":"64","author":"Choi","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.5142\/jgr.2012.36.3.225","article-title":"Ginseng in traditional herbal prescriptions","volume":"36","author":"Park","year":"2012","journal-title":"J. Ginseng Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.foodchem.2005.09.002","article-title":"Antioxidant activities of Salvia miltiorrhiza and Panax notoginseng","volume":"99","author":"Zhao","year":"2006","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9595","DOI":"10.1021\/jf301372g","article-title":"Ginsenoside Re ameliorates inflammation by inhibiting the binding of lipopolysaccharide to TLR4 on macrophages","volume":"60","author":"Lee","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0140-6736(04)16627-0","article-title":"Investigation of multipotent postnatal stem cells from human periodontal ligament","volume":"364","author":"Seo","year":"2004","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4049\/jimmunol.160.1.403","article-title":"IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis","volume":"160","author":"Assuma","year":"1998","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhu, W., and Liang, M. (2015). Periodontal ligament stem cells: Current status, concerns, and future prospects. Stem Cells Int., 972313.","DOI":"10.1155\/2015\/972313"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/jcp.25067","article-title":"Potential for stem cell-based periodontal therapy","volume":"231","author":"Bassir","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s00418-012-0923-6","article-title":"Human periodontal ligament fibroblasts are the optimal cell source for induced pluripotent stem cells","volume":"137","author":"Nomura","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1471-4906(03)00181-9","article-title":"Heme oxygenase-1: Unleashing the protective properties of heme","volume":"24","author":"Otterbein","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-0765.1991.tb01649.x","article-title":"The role of inflammatory mediators in the pathogenesis of periodontal disease","volume":"26","author":"Page","year":"1991","journal-title":"J. Periodontal. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ejphar.2011.08.008","article-title":"Anti-inflammatory effects of lindenenyl acetate via heme oxygenase-1 and AMPK in human periodontal ligament cells","volume":"670","author":"Jeong","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"153107","DOI":"10.1016\/j.phymed.2019.153107","article-title":"Effect of gomisin A on osteoblast differentiation in high glucose-mediated oxidative stress","volume":"66","author":"Takanche","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_28","first-page":"7","article-title":"Bone biomarkers in periodontal disease: A review article","volume":"9","author":"Ram","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1242\/jcs.00866","article-title":"Runx2 deficiency in chondrocytes causes adipogenic changes in vitro","volume":"117","author":"Enomoto","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3746\/jkfn.2011.40.2.229","article-title":"Quality characteristics of 4 year-old ginseng by enzymatic hydrolysis conditions","volume":"40","author":"Im","year":"2011","journal-title":"J. Korean Soc. Food Sci. Nutr."},{"key":"ref_31","first-page":"41","article-title":"Enzymatic hydrolysis of korean ginseng starch and characteristics of produced maltooligosaccharides","volume":"24","author":"Kim","year":"2000","journal-title":"J. Ginseng Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.4014\/jmb.1808.08052","article-title":"Inhibitory Effect of Standardized Curcuma xanthorrhiza Supercritical Extract on LPS-Induced Periodontitis in Rats","volume":"28","author":"Kook","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/JPER.19-0228","article-title":"6-Shogaol, an active ingredient of ginger, inhibits osteoclastogenesis and alveolar bone resorption in ligature-induced periodontitis in mice","volume":"91","author":"Kim","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"104529","DOI":"10.1016\/j.archoralbio.2019.104529","article-title":"Inhibitory effect of Acer tegmentosum maxim extracts on P. gingivalis LPS induced Periodontitis","volume":"109","author":"Choi","year":"2020","journal-title":"Arch. Oral Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1902\/jop.2012.120460","article-title":"The Effects of a Novel Botanical Agent on Lipopolysaccharide-Induced Alveolar Bone Loss in Rats","volume":"84","author":"Lee","year":"2013","journal-title":"J. Periodontol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/12\/1221\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:40:58Z","timestamp":1760179258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/12\/1221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["antiox9121221"],"URL":"https:\/\/doi.org\/10.3390\/antiox9121221","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]}}}