{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:49:57Z","timestamp":1787503797835,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medibio Lab Co., Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This study investigated the efficacy and safety of a propolis\u2013mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p &lt; 0.0001) at 8 weeks, including substantial reductions in IL-1\u03b2, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.<\/jats:p>","DOI":"10.3390\/nu16173000","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:44:29Z","timestamp":1725518669000},"page":"3000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Clinical Effect of a Propolis and Mangosteen Extract Complex in Subjects with Gingivitis: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial"],"prefix":"10.3390","volume":"16","author":[{"given":"Jae-Suk","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heelim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-9156","authenticated-orcid":false,"given":"Youngkyung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Dentistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-6731","authenticated-orcid":false,"given":"Suk","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-237X.118354","article-title":"Estimation of prostaglandin E2 levels in gingival crevicular fluid in periodontal health, disease and after treatment","volume":"4","author":"Kumar","year":"2013","journal-title":"Contemp. Clin. Dent."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.tibtech.2018.05.013","article-title":"Point-of-Care Periodontitis Testing: Biomarkers, Current Technologies, and Perspectives","volume":"36","author":"He","year":"2018","journal-title":"Trends Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.archoralbio.2012.11.012","article-title":"Profiling Biomarkers in Gingival Crevicular Fluid Using Multiplex Bead Immunoassay","volume":"58","author":"Shimada","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1600-051X.1990.tb01059.x","article-title":"Absence of bleeding on probing an indicator of periodontal stability","volume":"17","author":"Lang","year":"1990","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1902\/jop.1996.67.6.555","article-title":"Indices to measure gingival bleeding","volume":"67","author":"Newbrun","year":"1996","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1600-051X.2010.01670.x","article-title":"Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis","volume":"38","author":"Buduneli","year":"2011","journal-title":"J. Clin. Periodontol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fatima, T., Khurshid, Z., Rehman, A., Imran, E., Srivastava, K.C., and Shrivastava, D. (2021). Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases. Molecules, 26.","DOI":"10.3390\/molecules26051208"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1034\/j.1600-0757.2003.03105.x","article-title":"Origin and function of the cellular components in gingival crevice fluid","volume":"31","author":"Delima","year":"2003","journal-title":"Periodontology 2000"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/jcpe.12479","article-title":"Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: An exploratory study","volume":"43","author":"Baeza","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_10","first-page":"432","article-title":"Modulation of Host PGE2 Secretion as a Determinant of Periodontal Disease Expression","volume":"64","author":"Offenbacher","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/jcpe.12194","article-title":"Crevicular fluid biomarkers and periodontal disease progression","volume":"41","author":"Kinney","year":"2014","journal-title":"J. Clin. Periodontol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, M., Baeza, M., R\u00e4is\u00e4nen, I.T., Contreras, J., Tervahartiala, T., Chaparro, A., Sorsa, T., and Hern\u00e1ndez-R\u00edos, P. (2021). Active MMP-8 Quantitative Test as an Adjunctive Tool for Early Diagnosis of Periodontitis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11081503"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1034\/j.1600-0757.2003.03110.x","article-title":"Potential for gingival crevice fluid measures as predictors of risk for periodontal diseases","volume":"31","author":"Champagne","year":"2003","journal-title":"Periodontology 2000"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1600-0757.2005.00129.x","article-title":"Host-derived diagnostic markers for periodontitis: Do they exist in gingival crevice fluid?","volume":"39","author":"Loos","year":"2005","journal-title":"Periodontology 2000"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1902\/jop.2005.76.11-S.2089","article-title":"Systemic Effects of Periodontitis: Epidemiology of Periodontal Disease and Cardiovascular Disease","volume":"76","author":"Beck","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.14219\/jada.archive.2006.0404","article-title":"Periodontal Disease and Diabetes: A Two-Way Street","volume":"137","author":"Mealey","year":"2006","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"230","DOI":"10.2174\/138161282202151221124307","article-title":"Periodontitis and Periodontal Disease\u2014Innovative Strategies for Reversing the Chronic Infectious and Inflammatory Condition by Natural Products","volume":"22","author":"Lazar","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/jre.12683","article-title":"Impact of Natural Curcumin on the Progression of Experimental Periodontitis in Diabetic Rats","volume":"55","author":"Pimentel","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.20473\/j.djmkg.v51.i3.p133-137","article-title":"Cytoxicity test of NaOCl and Mangosteen (Garcinia mangostin L.) peel extract used as an irrigation solution in human periodontal ligament fibroblast cells (HPdLFc)","volume":"51","author":"Yuanita","year":"2018","journal-title":"Dent. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3892\/ijmm.2016.2517","article-title":"Antitumor and apoptosis-inducing effects of \u03b1-mangostin extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.) in YD-15 tongue mucoepidermoid carcinoma cells","volume":"37","author":"Lee","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/S0367-326X(02)00186-7","article-title":"Analytical Methods for Quality Control of Propolis","volume":"73","author":"Pietta","year":"2002","journal-title":"Fitoterapia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.canlet.2011.04.012","article-title":"Caffeic Acid Phenethyl Ester (CAPE), Derived from a Honeybee Product Propolis, Exhibits a Diversity of Anti-Tumor Effects in Pre-Clinical Models of Human Breast Cancer","volume":"308","author":"Wu","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"296186","DOI":"10.1155\/2015\/296186","article-title":"Antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities of propolis from the stingless Bee Tetragonisca fiebrigi (Jata\u00ed)","volume":"2015","author":"Campos","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10068-019-00697-3","article-title":"Anti-inflammatory and in vitro bone formation effects of Garcinia mangostana L. and propolis extracts","volume":"29","author":"Lim","year":"2020","journal-title":"Food Sci. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.11620\/IJOB.2019.44.2.55","article-title":"Effect of Garcinia mangostana L. and Propolis Extracts on the Inhibition of Inflammation and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats","volume":"44","author":"Sung","year":"2019","journal-title":"Int. J. Oral Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.14815\/kjdm.2021.48.2.71","article-title":"Inhibitory effect of mangosteen peel and propolis ethanol extracts on alveolar bone loss against increased treatment amount of Porphyromonas gingivalis lipopolysaccharide in rat","volume":"48","author":"Lee","year":"2021","journal-title":"Korean J. Dent. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3109\/00016356309011240","article-title":"Periodontal Disease in Pregnancy I. Prevalence and Severity","volume":"21","author":"Silness","year":"1963","journal-title":"Acta. Odontol. Scand."},{"key":"ref_28","first-page":"41","article-title":"Reduced Plaque Formation by the Chloromethyl Analogue of Vitamin C","volume":"41","author":"Turesky","year":"1970","journal-title":"J. Periodontol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10266-019-00435-5","article-title":"Relationship between TNF-\u03b1, MMP-8, and MMP-9 Levels in Gingival Crevicular Fluid and the Subgingival Microbiota in Periodontal Disease","volume":"108","year":"2020","journal-title":"Odontology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1126\/science.6254151","article-title":"Prostaglandins, arachidonic acid, and inflammation","volume":"210","author":"Kuehl","year":"1980","journal-title":"Science"},{"key":"ref_31","first-page":"407","article-title":"Biochemical and molecular mediators of bone metabolism","volume":"64","author":"Dziak","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/154405910608500110","article-title":"Gingival tissue and crevicular fluid co-operation in adult periodontitis","volume":"85","author":"Beklen","year":"2006","journal-title":"J. Dent. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1039\/C8FO00439K","article-title":"An anti-inflammatory molecular mechanism of action of \u03b1-mangostin, the major xanthone from the pericarp of Garcinia mangostana: An in silico, in vitro and in vivo approach","volume":"9","author":"Mohan","year":"2018","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"893","DOI":"10.4103\/ijdr.IJDR_909_19","article-title":"Effect of local propolis irrigation in experimental periodontitis in rats on inflammatory markers (IL-1\u03b2 and TNF-\u03b1) and oxidative stress","volume":"31","author":"Ali","year":"2020","journal-title":"Indian J. Dent. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luchian, I., Goriuc, A., Sandu, D., and Covasa, M. (2022). The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031806"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.34172\/japid.2021.013","article-title":"Effect of propolis extract on clinical parameters and salivary level of matrix metalloproteinase 8 in periodontitis patients: A randomized controlled clinical trial","volume":"13","author":"Askari","year":"2021","journal-title":"J. Adv. Periodontol. Implant Dent."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jclinepi.2013.08.015","article-title":"Systematic review of the Hawthorne effect: New concepts are needed to study research participation effects","volume":"67","author":"McCambridge","year":"2014","journal-title":"J. Clin. Epidemiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Buduneli, N. (2019). Biomarkers in Periodontal Health and Disease: Rationale, Benefits, and Future Directions, Springer.","DOI":"10.1007\/978-3-030-37317-7"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1600-051X.1993.tb01760.x","article-title":"Evaluation of reliability and reproducibility of dental indices","volume":"20","author":"Marks","year":"1993","journal-title":"J. Clin. Periodontol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1600-0757.1996.tb00078.x","article-title":"Manual periodontal probing in supportive periodontal treatment","volume":"12","author":"Armitage","year":"1996","journal-title":"Periodontology 2000"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1902\/jop.1992.63.4.283","article-title":"Comparison of Measurement Variability in Subjects with Moderate Periodontitis Using a Conventional and Constant Force Periodontal Probe","volume":"63","author":"Osborn","year":"1992","journal-title":"J. Periodontol."},{"key":"ref_42","first-page":"1804727","article-title":"Identification of gingival crevicular fluid sampling, analytical methods, and oral biomarkers for the diagnosis and monitoring of periodontal diseases: A systematic review","volume":"2016","author":"Philip","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_43","first-page":"7891323","article-title":"Matrix Metalloproteinase-8 as an Inflammatory and Prevention Biomarker in Periodontal and Peri-Implant Diseases","volume":"2018","author":"Alassiri","year":"2018","journal-title":"Int. J. Dent."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.clinbiochem.2008.04.013","article-title":"Gingival crevicular fluid PGE2, IL-1beta, t-PA, PAI-2 levels in type 2 diabetes and relationship with periodontal disease","volume":"41","author":"Buduneli","year":"2008","journal-title":"Clin. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.sdentj.2010.04.006","article-title":"Levels of Gingival Crevicular Metalloproteinases-8 and -9 in Periodontitis","volume":"22","author":"Rai","year":"2010","journal-title":"Saudi Dent. J."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3000\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:11Z","timestamp":1760111351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":45,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16173000"],"URL":"https:\/\/doi.org\/10.3390\/nu16173000","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}