{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T22:21:57Z","timestamp":1769725317559,"version":"3.49.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Earth Corporation"},{"name":"Earth Corporation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Recurrent aphthous stomatitis (RAS), a major type of stomatitis, can significantly impair quality of life. The therapeutic and preventive effects of glycyrrhizin (GL), a compound known for its anti-inflammatory properties, remain unclear due to the lack of appropriate animal models, especially for prevention studies. Therefore, this study aimed to evaluate the therapeutic and preventive effects of GL and determine the optimal concentrations using two hamster models (stomatitis-initiation model and stomatitis-healing model) representing the initiation and healing phases of RAS. The effects were evaluated through macroscopic and histological analyses, gene expression profiling in hamster buccal tissues, and prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) assays in lipopolysaccharide-stimulated human oral keratinocytes. In the stomatitis-healing model, a low concentration of GL (0.0065%) significantly increased the cure rate and histologically reduced the numbers of vessels and lymphocytes. In the stomatitis-initiation model, low concentrations of GL (0.0065% and 0.033%) significantly decreased the edema score and histologically reduced the numbers of vessels and neutrophils, as well as the mRNA expression levels of\n                    <jats:italic>interleukin-6<\/jats:italic>\n                    and\n                    <jats:italic>cyclooxygenase-2<\/jats:italic>\n                    . In contrast, a high concentration of GL (0.33%) showed inferior efficacy compared with low concentrations in both models. Similarly, in LPS-stimulated human oral keratinocytes, low GL concentrations suppressed PGE\u2082 protein expression, while the highest concentration increased it. These findings show that GL promotes healing and prevents the onset of stomatitis at specific concentrations, underscoring the importance of optimal dosing and supporting the potential clinical application of GL in the management of RAS.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0338806","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:27:41Z","timestamp":1768588061000},"page":"e0338806","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of glycyrrhizin on healing and prevention of recurrent aphthous stomatitis in hamster models"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-5750","authenticated-orcid":true,"given":"Fumie","family":"Shiba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiiko","family":"Maekawara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisako","family":"Furusho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eri","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Shigeishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouji","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-9703","authenticated-orcid":true,"given":"Mutsumi","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"pone.0338806.ref001","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.critrevonc.2016.01.010","article-title":"Mucositis in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus statements","volume":"100","author":"V De Sanctis","year":"2016","journal-title":"Crit Rev Oncol Hematol"},{"issue":"3","key":"pone.0338806.ref002","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejon.2014.12.001","article-title":"Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment","volume":"19","author":"S-C Chen","year":"2015","journal-title":"Eur J Oncol Nurs"},{"key":"pone.0338806.ref003","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fphar.2017.00354","article-title":"New Frontiers in the Pathobiology and Treatment of Cancer Regimen-Related Mucosal Injury","volume":"8","author":"M Cinausero","year":"2017","journal-title":"Front Pharmacol"},{"issue":"4","key":"pone.0338806.ref004","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.anai.2016.07.005","article-title":"Aphthous stomatitis","volume":"117","author":"K Shah","year":"2016","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"4","key":"pone.0338806.ref005","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S1808-8694(15)30110-5","article-title":"Radiation therapy and chemotherapy-induced oral mucositis","volume":"73","author":"LER Volpato","year":"2007","journal-title":"Braz J Otorhinolaryngol"},{"issue":"3","key":"pone.0338806.ref006","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1006\/ijom.2002.0446","article-title":"Recurrent aphthous ulcers today: a review of the growing knowledge","volume":"33","author":"SS Natah","year":"2004","journal-title":"Int J Oral Maxillofac Surg"},{"issue":"6","key":"pone.0338806.ref007","article-title":"Recurrent aphthous stomatitis: A comprehensive review and recommendations on therapeutic options","volume":"35","author":"CB Lau","year":"2022","journal-title":"Dermatol Ther"},{"issue":"2","key":"pone.0338806.ref008","article-title":"Treatment of recurrent aphthous stomatitis. 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