• ANIS NUR RAMDHIANI Bachelor Program in Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Indonesia
  • WAHYU HIDAYAT Departement of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Indonesia
  • INDAH SUASANI WAHYUNI Departement of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Indonesia



Oral mucositis, Propolis, Chemotherapy, Radiotherapy


Oral mucositis (OM) is an oral mucosal inflammation and complication of chemotherapy and/or radiotherapy. One of the natural agents that has been widely studied as an alternative therapy for OM was Propolis. This review aims to analyze the effectiveness and safety of propolis and its mechanism of action in preventing and treating OM through clinical study in human and animal models. Articles searched using the keywords “Oral Mucositis” AND “Propolis”, conducted through PubMed, ScienceDirect, and Cochrane Library databases. The inclusion criteria were: Clinical Trial and Animal Study design; in English; full paper available; published between 2016-2021; and high range of quality and articles in line to the research topic. RoB-tools JADAD Oxford Quality Scoring System and SYRCLE’s RoB tool was used for risk of bias determination. This paper writing refers to PRISMA guidelines. In vivo studies and clinical trials have shown that propolis can reduce OM Index scores in animals or OM grades in patients. Propolis can also reduce the symptoms of inflammation in OM and almost all articles stated that there were no side effects of propolis for oral mucositis. In vivo studies showed that propolis was able to inhibit pro-inflammatory markers, hypoxia markers, MPO serum levels, and TNF-alpha cytokines, but increased the expression of pS6, pAKT, NF-B, and GSH. Propolis is effective and safe to use in patients receiving chemotherapy/radiotherapy to prevent the severity and potential for OM therapy. The mechanism of action of propolis in overcoming clinical symptoms of OM is as an anti-inflammatory, antioxidant, and helps accelerate wound healing.


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Munstedt K, Mannle H. Using bee products for the prevention and treatment of oral mucositis induced by cancer treatment. Molecules. 2019;24(17). doi: 10.3390/molecules24173023, PMID 31438508.

Pulito C, Cristaudo A, La Porta C, Zapperi S, Blandino G, Morrone A. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res. 2020;39(1):210. doi: 10.1186/s13046-020-01715-7, PMID 33028357.

Lalla RV, Saunders DP, Peterson DE. Chemotherapy or radiation-induced oral mucositis. Dent Clin North Am. 2014;58(2):341-9. doi: 10.1016/j.cden.2013.12.005, PMID 24655526.

Daugelaite G, Uzkuraityte K, Jagelavicienc E, Filipauskas A. Prevention and treatment of chemotherapy and radiotherapy induced oral mucositis. Medicina (Kaunas). 2019;55(2):1-14. doi: 10.3390/medicina55020025, PMID 30678228.

Tomazevic T, Jazbec J. A double blind randomised placebo controlled study of propolis (bee glue) effectiveness in the treatment of severe oral mucositis in chemotherapy treated children. Complement Ther Med. 2013;21(4):306-12. doi: 10.1016/j.ctim.2013.04.002, PMID 23876561.

Piredda M, Facchinetti G, Biagioli V, Giannarelli D, Armento G, Tonini G. Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: a pilot randomised controlled trial. Eur J Cancer Care (Engl). 2017;26(6):1-8. doi: 10.1111/ecc.12757, PMID 28840622.

Wahyuni IS, Sufiawati I, Nittayananta W, Puspitasari IM, Levita J. Efficacy and safety of plant-based therapy on recurrent aphthous stomatitis and oral mucositis in the past decade: a systematic review. J Herb Med Pharmacol. 2021;10(2):179-87. doi: 10.34172/jhp.2021.19.

Marcucci MC, Ferreres F, Garcia Viguera C, Bankova VS, De Castro SL, Dantas AP. Phenolic compounds from Brazilian propolis with pharmacological activities. J Ethnopharmacol. 2001;74(2):105-12. doi: 10.1016/s0378-8741(00)00326-3, PMID 11167028.

Wagh VD. Propolis: A wonder bees product and its pharmacological potentials. Adv Pharmacol Sci. 2013;2013:308249. doi: 10.1155/2013/308249, PMID 24382957.

Zulhendri F, Felitti R, Fearnley J, Ravalia M. The use of propolis in dentistry, oral health, and medicine: a review. J Oral Biosci. 2021;63(1):23-34. doi: 10.1016/j.job.2021.01.001. PMID 33465498.

Tamfu AN, Sawalda M, Fotsing MT, Kouipou RMT, Talla E, Chi GF. A new isoflavones and other constituents from Cameroonian propolis and evaluation of their anti-inflammatory, antifungal and antioxidant potential. Saudi J Biol Sci. 2020;27(6):1659-66. doi: 10.1016/j.sjbs.2019.11.035, PMID 32489308. sjbs.2019.11.035.

Zaccaria V, Curti V, Di Lorenzo A, Baldi A, Maccario C, Sommatis S. Effect of green and brown propolis extracts on the expression levels of microRNAs, mRNAs and proteins, related to oxidative stress and inflammation. Nutrients. 2017;9(10):1-17. doi: 10.3390/nu9101090.

Zhang W, Cai Y, Chen X, Ji T, Sun L. Optimized extraction based on the terpenoids of Heterotrigona itama propolis and their antioxidative and anti-inflammatory activities. J Food Biochem. 2020;44(8):e13296. doi: 10.1111/jfbc.13296, PMID 32529646.

Khayyal MT, Abdel-Naby DH, El-Ghazaly MA. Propolis extract protects against radiation-induced intestinal mucositis through anti-apoptotic mechanisms. Environ Sci Pollut Res Int. 2019;26(24):24672-82. doi: 10.1007/s11356-019-05782-y, PMID 31240658.

Avci E, Akarslan ZZ, Erten H, Coskun Cevher S. Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers. Braz J Med Biol Res. 2014;47(5):355-60. doi: 10.1590/1414-431x20143714, PMID 24760117.

Eslami H, Pouralibaba F, Falsafi P, Bohluli S, Najati B, Negahdari R. Efficacy of Hypozalix spray and propolis mouthwash for prevention of chemotherapy-induced oral mucositis in leukemic patients: a double-blind randomized clinical trial. J Dent Res Dent Clin Dent Prospects. 2016;10(4):226-33. doi: 10.15171/joddd.2016.036, PMID 28096948.

Dastan F, Ameri A, Dodge S, Hamidi Shishvan H, Pirsalehi A, Abbasinazari M. Efficacy and safety of propolis mouthwash in management of radiotherapy-induced oral mucositis: A randomized, double blind clinical trial. Rep Pract Oncol Radiother. 2020;25(6):969-73. doi: 10.1016/j.rpor.2020.09.012, PMID 33100913.

Marucci L, Farneti A, Di Ridolfi P, Pinnaro P, Pellini R, Giannarelli D. Double-blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer. Head Neck. 2017;39(9):1761-9. doi: 10.1002/hed.24832, PMID 28560780.

VRAS N, EN A FPCL P, VR S. Propolis gel versus benzydamine in preventing oral mucositis for patients irradiated in head and neck: a preliminary study. Cancer Rep Rev. 2017;1(2):1-4.

Salehi M, Saeedi M, Ghorbani A, Ghodrati P, Moosazadeh M, Rostamkalaei S. The effect of propolis tablet on oral mucositis caused by chemotherapy. Gazi Med J. 2018;29(3):196-201.

Kuo CC, Wang RH, Wang HH, Li CH. Meta-analysis of randomized controlled trials of the efficacy of propolis mouthwash in cancer therapy-induced oral mucositis. Support Care Cancer. 2018;26(12):4001-9. doi: 10.1007/s00520-018-4344-5, PMID 30022350.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLOS Med. 2021;18(3):e1003583. doi: 10.1371/journal.pmed.1003583, PMID 33780438.

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12. doi: 10.1016/0197-2456(95)00134-4, PMID 8721797.

Hooijmans CR, Rovers MM, De Vries RBM, Leenaars M, Ritskes Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14(1):43. doi: 10.1186/1471-2288-14-43, PMID 24667063.

Nistor M, Schmidt M, Graul I, Rakers F, Schiffner R. A systematic review of neuroprotective strategies in the management of hypoglycemia. Int J Mol Sci. 2019;20(3). doi: 10.3390/ijms20030550, PMID 30696060.

Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77-101. doi: 10.1191/1478088706qp063oa.

Akhavan Karbassi MH, Yazdi MF, Ahadian H, Sadr Abad MJ. Randomized double-blind placebo-controlled trial of propolis for oral mucositis in patients receiving chemotherapy for head and neck cancer Ensayo aleatorizado doble ciego controlado con placebo de propoleopara la mucositis oral en pacientes que reciben q. Asian Pac J Cancer Prev. 2016;17(7):3611-4.

Guler Avci G, Erdim I, Ozmen ZC, Gevrek F, Colak S, Demirsoy MS. The effect of systemic application of propolis on tongue damage and oral mucositis in rats exposed to radiation. Eur Arch Otorhinolaryngol. 2022;279(2):1043-52. doi: 10.1007/s00405-021-07159-9, PMID 34746967.

Severo MLB, Thieme S, Silveira FM, Tavares RPM, Gonzaga AKG, Zucolotto SM. Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats. Support Care Cancer. 2022;30(3):2723-34. doi: 10.1007/s00520-021-06660-5. PMID 34822003.

Lalla RV, Brennan MT, Gordon SM, Sonis ST, Rosenthal DI, Keefe DM. Oral mucositis due to high-dose chemotherapy and/or head and neck radiation therapy. J Natl Cancer Inst Monogr. 2019;2019(53):17-24. doi: 10.1093/jncimonographs/ lgz011, PMID 31425601.

Charalambous M, Raftopoulos V, Paikousis L, Katodritis N, Lambrinou E, Vomvas D. The effect of the use of thyme honey in minimizing radiation-induced oral mucositis in head and neck cancer patients: A randomized controlled trial. Eur J Oncol Nurs. 2018;34(April):89-97. doi: 10.1016/j.ejon.2018.04.003. PMID 29784145.

Chandna P, Adlakha V, Das S, Singh S. Complementary and alternative medicine (CAM): a review of propolis in dentistry. Am J Phytomed Clin Ther. 2014;2(6):670-85.

Santos LM, Fonseca MS, Sokolonski AR, Deegan KR, Araujo RPC, Umsza Guez MA. Propolis: types, composition, biological activities, and veterinary product patent prospecting. J Sci Food Agric. 2020;100(4):1369-82. doi: 10.1002/jsfa.10024, PMID 31487405.

Anjum SI, Ullah A, Khan KA, Attaullah M, Khan H, Ali H. Composition and functional properties of propolis (bee glue): a review. Saudi J Biol Sci. 2019;26(7):1695-703. doi: 10.1016/j.sjbs.2018.08.013, PMID 31762646.

Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J. Phase II double-blind, randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. Int J Radiat Oncol Biol Phys. 2004;60(1):171-7. doi: 10.1016/j.ijrobp.2004.02.012, PMID 15337553.

Wahyuni Is SI, Nittayananta W, Levita J. Original article the determination of ethyl P-methoxy cinnamate in Kaempferia Galanga L. Rhizome extract harvested in rainy and dry seasons. Vol. 13(4); 2021.



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