{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:49:18Z","timestamp":1791348558398,"version":"4.3.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall \u2018high risk\u2019 of bias, while the remaining studies were categorised as having an overall \u2018uncertain risk\u2019. The overall certainty of the evidence was \u2018very low\u2019. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS.<\/jats:p>","DOI":"10.3390\/dj12010013","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T03:49:04Z","timestamp":1704685744000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and Safety of Propolis for Treating Recurrent Aphthous Stomatitis (RAS): A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Tina","family":"Roberts","sequence":"first","affiliation":[{"name":"Department of Craniofacial Biology, Pathology and Radiology, Faculty of Dentistry, University of the Western Cape, Cape Town 7500, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idriss Ibrahim","family":"Kallon","sequence":"additional","affiliation":[{"name":"Centre for Evidence-Based Health Care, Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7500, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anel","family":"Schoonees","sequence":"additional","affiliation":[{"name":"Centre for Evidence-Based Health Care, Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7500, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0030-4220(72)90470-7","article-title":"Aphthous lesions","volume":"33","author":"Stanley","year":"1972","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_2","unstructured":"Mehdipour, M., and Taghavi, A. (2022, February 08). Role of Corticosteroids in Oral Lesions. State Art Ther Endocrinol [Internet]. Available online: https:\/\/www.intechopen.com\/chapters\/39492."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dalessandri, D., Zotti, F., Laffranchi, L., Migliorati, M., Isola, G., Bonetti, S., and Visconti, L. (2019). Treatment of recurrent aphthous stomatitis (RAS; aphthae; canker sores) with a barrier forming mouth rinse or topical gel formulation containing hyaluronic acid: A retrospective clinical study. BMC Oral Health, 19.","DOI":"10.1186\/s12903-019-0850-1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2021099","DOI":"10.5826\/dpc.1104a99","article-title":"Recurrent aphthous stomatitis: Treatment and management","volume":"11","author":"Manfredini","year":"2021","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1600-0714.1989.tb00727.x","article-title":"Recurrent aphthous stomatitis: Current concepts of etiology, pathogenesis and management","volume":"18","author":"Scully","year":"1989","journal-title":"J. Oral Pathol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.23736\/S0026-4970.18.04135-3","article-title":"Behcet\u2019s disease: Minireview with emphasis on oral aspects","volume":"67","author":"Giannetti","year":"2018","journal-title":"Minerva Stomatol."},{"key":"ref_7","first-page":"47","article-title":"Essentials of recurrent aphthous stomatitis","volume":"11","author":"Rivera","year":"2019","journal-title":"Biomed. Rep."},{"key":"ref_8","first-page":"205","article-title":"Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: Literature review","volume":"62","author":"Szponar","year":"2013","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1600-0528.2007.00329.x","article-title":"Risk indicators for recurrent aphthous ulcers among adults in the US","volume":"35","author":"Chattopadhyay","year":"2007","journal-title":"Community Dent. Oral Epidemiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/jop.12059","article-title":"Clinical assessment of disease severity in recurrent aphthous stomatitis","volume":"42","author":"Tappuni","year":"2013","journal-title":"J. Oral Pathol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/j.1600-0714.2008.00661.x","article-title":"Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitis","volume":"37","author":"Lewkowicz","year":"2008","journal-title":"J. Oral Pathol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1034\/j.1600-0714.2000.290104.x","article-title":"Immunolocalisation of tumor necrosis factor-\u03b1 expressing cells in recurrent aphthous ulcer lesions (RAU)","volume":"29","author":"Natah","year":"2000","journal-title":"J. Oral Pathol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.0904-2512.2004.00089.x","article-title":"The Th1\/Th2 immune-type response of the recurrent aphthous ulceration analysed by cDNA microarray","volume":"33","author":"Borra","year":"2004","journal-title":"J. Oral Pathol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1080\/03009740600905380","article-title":"Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet\u2019s disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD","volume":"35","author":"Dalghous","year":"2006","journal-title":"Scand. J. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.17126\/joralres.2017.069","article-title":"Immune system and zinc are associated with recurrent aphthous stomatitis. An assessment using a network-based approach","volume":"6","author":"Rivera","year":"2017","journal-title":"J. Oral Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111064","DOI":"10.18632\/oncotarget.22347","article-title":"Systemic bioinformatics analysis of recurrent aphthous stomatitis gene expression profiles","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1259510","DOI":"10.1155\/2017\/1259510","article-title":"Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits","volume":"2017","author":"Pasupuleti","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.phymed.2004.07.008","article-title":"In vitro effects of propolis on Giardia duodenalis trophozoites","volume":"13","author":"Freitas","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Olczyk, P., Komosinska-Vassev, K., Wisowski, G., Mencner, L., Stojko, J., and Kozma, E.M. (2014). Propolis modulates fibronectin expression in the matrix of thermal injury. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/748101"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3390\/molecules25030556","article-title":"Bee products in dermatology and skin care","volume":"25","author":"Balwierz","year":"2020","journal-title":"Molecules"},{"key":"ref_21","first-page":"167","article-title":"Effectiveness of propolis in maintaining oral health: A scoping review","volume":"55","author":"Saeed","year":"2021","journal-title":"Canadian Journal of Dental Hygiene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.sjbs.2018.08.013","article-title":"Composition and functional properties of propolis (bee glue): A review","volume":"26","author":"Anjum","year":"2019","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1046\/j.1365-2036.2003.01782.x","article-title":"Review article: Oral ulceration\u2014Aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic","volume":"18","author":"Field","year":"2003","journal-title":"Aliment. Pllarmacology Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s11655-016-2748-y","article-title":"Prevalence and Determinants of Traditional, Complementary and Alternative Medicine Provider Use among Adults from 32 Countries","volume":"24","author":"Peltzer","year":"2016","journal-title":"Chin. J. Integr. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_26","unstructured":"Higgins, J.P., Savovi\u0107, J., Page, M.J., Elbers, R.G., and Sterne, J.A. (2022, February 08). Chapter 8: Assessing Risk of Bias in a Randomised Trial|Cochrane Training. Cochrane Training [Internet]. Available online: https:\/\/training.cochrane.org\/handbook\/current\/chapter-08."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","article-title":"GRADE guidelines: 1. Introduction\u2014GRADE evidence profiles and summary of findings tables","volume":"64","author":"Guyatt","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jclinepi.2019.10.014","article-title":"GRADE guidelines 26: Informative statements to communicate the findings of systematic reviews of interventions","volume":"119","author":"Santesso","year":"2020","journal-title":"J. Clin. Epidemiol."},{"key":"ref_29","unstructured":"(2022, April 15). Review Manager (RevMan) [Computer Program]. Version 5.4. Available online: https:\/\/training.cochrane.org\/online-learning\/core-software\/revman."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.33899\/rden.2003.165763","article-title":"Aqueous extract of propolis in the treatment of recurrent aphthous stomatitis (Double blind study)","volume":"3","year":"2003","journal-title":"Al-Rafidain Dent. J."},{"key":"ref_31","first-page":"29","article-title":"Propolis buccal paste in treatment of aphthous ulceration: Formulation and clinical evaluation","volume":"4","author":"Ali","year":"2011","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1515\/prilozi-2015-0024","article-title":"The rapeutic effect of proaftol in treatment of recurrent aphthous stomatitis","volume":"35","author":"Stojanovska","year":"2014","journal-title":"Prilozi"},{"key":"ref_33","first-page":"691","article-title":"mean days of healin mean pain score Degree of erythema Efficacy of honey in comparison to topical corticosteroid for treatment of recurrent minor aphthous ulceration: A randomised, blind, controlled, parallel, double-center clinical trial","volume":"45","author":"Asiri","year":"2014","journal-title":"Quintessence Int."},{"key":"ref_34","first-page":"211","article-title":"Efficacy of propolis mouth wash for treatment of recurrent aphthous stomatitis","volume":"3","author":"Tonkaboni","year":"2016","journal-title":"J. Craniomaxillofacial Res. Summer"},{"key":"ref_35","first-page":"55","article-title":"Randomised clinical trial of the effectiveness of complementary therapies for recurrent aphthous stomatitis","volume":"149","author":"Raissouni","year":"2017","journal-title":"Med. Cl\u00ednica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.52547\/jorjanibiomedj.10.1.56","article-title":"Effects of Propolis and Persica Mouthwashes on Minor Aphthous Ulcers: A Comparative Study","volume":"10","author":"Alemrajabi","year":"2022","journal-title":"Jorjani Biomed. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00784-006-0090-z","article-title":"The effect of bee propolis on recurrent aphthous stomatitis: A pilot study","volume":"11","author":"Samet","year":"2007","journal-title":"Clin. Oral Investig."},{"key":"ref_38","first-page":"143","article-title":"Effectiveness of Bee Propolis on Recurrent Aphthous Stomatitis: A Randomised Clinical Trial","volume":"10","author":"Delavarian","year":"2015","journal-title":"Res. J. Fish Hydrobiol."},{"key":"ref_39","first-page":"1176","article-title":"60 cases of Aphthous ulcer treated with Pujia propolis tablets Yanhui","volume":"35","author":"Liu","year":"2015","journal-title":"Henan Tradit Chin. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.9734\/jpri\/2022\/v34i43B36326","article-title":"Meta-analysis on the Effectiveness and Safety of Propolis Preparation in the Treatment of Aphthous Ulcers","volume":"34","author":"Jinlong","year":"2022","journal-title":"J. Pharm. Res. Int."}],"container-title":["Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-6767\/12\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:41:19Z","timestamp":1760103679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-6767\/12\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,6]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["dj12010013"],"URL":"https:\/\/doi.org\/10.3390\/dj12010013","relation":{},"ISSN":["2304-6767"],"issn-type":[{"value":"2304-6767","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,6]]}}}