{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T18:07:08Z","timestamp":1779991628646,"version":"3.53.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008040","name":"Kao Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    \u03b2-glycyrrhetinic acid (BGA) possesses antibacterial effects against human supragingival plaque bacteria and inhibits\u00a0biofilm formation. However, the effect of BGA on already formed dental plaque has not been investigated. We analyzed and compared the effects of BGA on preformed supragingival plaque biofilms with those of cetylpyridinium chloride (CPC). All experiments were performed\n                    <jats:italic>in vitro<\/jats:italic>\n                    using biofilms formed by incubating supragingival plaque bacteria for 24\u2009h. First, we analyzed the number of viable and dead bacteria in the biofilms following BGA and CPC application. The number of viable bacteria was significantly reduced by BGA treatment compared with by the solvent control. However, the viable\/dead bacterial ratios did not significantly vary. Conversely, the turbidity in the supernatants (optical density at 600\u2009nm [OD\n                    <jats:sub>600<\/jats:sub>\n                    ]) was 0.237\u2009\u00b1\u20090.003, 0.136\u2009\u00b1\u20090.002, and 0.096\u2009\u00b1\u20090.002 for the BGA, CPC, and solvent control groups, respectively, indicating superior ability of BGA in biofilm exfoliation. This study suggests that BGA may inhibit dental plaque adhesion and eliminate and disinfect dental plaque through a mechanism different from CPC, contributing to the prevention of periodontal disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0348495","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T17:44:01Z","timestamp":1779990241000},"page":"e0348495","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exfoliating effect of \u03b2-glycyrrhetinic acid on plaque inducing gingivitis: Comparison with cetylpyridinium chloride"],"prefix":"10.1371","volume":"21","author":[{"given":"Shinya","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Yoshinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-9022","authenticated-orcid":true,"given":"Akihiro","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"issue":"7203","key":"pone.0348495.ref001","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"R Medzhitov","year":"2008","journal-title":"Nature"},{"issue":"2","key":"pone.0348495.ref002","doi-asserted-by":"crossref","first-page":"882","DOI":"10.3390\/ijms23020882","article-title":"Armed to the Teeth-The Oral Mucosa Immunity System and Microbiota","volume":"23","author":"M Ptasiewicz","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"8","key":"pone.0348495.ref003","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1177\/0022034516645564","article-title":"Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States","volume":"95","author":"N Fine","year":"2016","journal-title":"J Dent Res"},{"issue":"10","key":"pone.0348495.ref004","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1902\/jop.1998.69.10.1139","article-title":"Neutrophil migration into the gingival sulcus is associated with transepithelial gradients of interleukin-8 and ICAM-1","volume":"69","author":"MS Tonetti","year":"1998","journal-title":"J Periodontol"},{"key":"pone.0348495.ref005","doi-asserted-by":"crossref","first-page":"1396106","DOI":"10.1155\/2016\/1396106","article-title":"Neutrophil Functions in Periodontal Homeostasis","volume":"2016","author":"R Cort\u00e9s-Vieyra","year":"2016","journal-title":"J Immunol Res"},{"issue":"7","key":"pone.0348495.ref006","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrmicro2337","article-title":"Periodontitis: a polymicrobial disruption of host homeostasis","volume":"8","author":"RP Darveau","year":"2010","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pone.0348495.ref007","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/prd.12371","article-title":"Polymicrobial communities in periodontal disease: Their quasi-organismal nature and dialogue with the host","volume":"86","author":"G Hajishengallis","year":"2021","journal-title":"Periodontol 2000"},{"key":"pone.0348495.ref008","article-title":"Plaque-induced gingivitis: Case definition and diagnostic considerations","author":"L Trombelli","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"27","key":"pone.0348495.ref009","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2012578118","article-title":"Human variation in gingival inflammation","volume":"118","author":"S Bamashmous","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0348495.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0765.1966.tb01842.x","article-title":"Experimental gingivitis in man. 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Oyama","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"pone.0348495.ref035","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1186\/s12903-025-06737-1","article-title":"\u03b2-glycyrrhetinic acid-containing dentifrice alleviates dental plaque accumulation and gingival inflammation: a randomized, cross-over, placebo-controlled study","volume":"25","author":"Y Yamashita","year":"2025","journal-title":"BMC Oral Health"},{"issue":"9","key":"pone.0348495.ref036","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/1348-0421.12884","article-title":"\u03b2-Glycyrrhetinic acid inhibits the bacterial growth and biofilm formation by supragingival plaque commensals","volume":"65","author":"N Dewake","year":"2021","journal-title":"Microbiol Immunol"},{"key":"pone.0348495.ref037","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical 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