Comparison of the Therapeutic Effects of 2% Areca catechu Gel and 0.1% Triamcinolone Acetonide in Patients with Recurrent Aphthous Stomatitis: A Randomized Clinical Trial
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Abstract
Areca catechu L. (A. catechu) or areca nut contains the main phytochemical compounds arecoline and catechin. It also possesses high antioxidant properties and can be used as a medication. Thus, this study was conducted to compare the therapeutic effects of 2% A. catechu gel and 0.1% triamcinolone acetonide on recurrent aphthous stomatitis (RAS). Overall, 46 randomly selected patients were divided into A. catechu gel and triamcinolone acetonide treatment groups. The topical preparations were applied to oral lesions three times daily in each group. Ulcer diameter, discoloration, pain intensity, and quality of life were assessed for 7 days, with ulcer size and pain intensity analyzed on day 7. Consequently, the A. catechu gel and triamcinolone acetonide demonstrated therapeutic effects after 7 days of treatment. The topical treatments examined did not show a significant difference in alleviating pain and reducing erythema associated with the ulcer. Furthermore, no correlation was found between ulcer diameter and pain intensity in A. catechu and triamcinolone acetonide. Areca catechu gel promoted RAS healing owing to its analgesic and anti-inflammatory properties.
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1. Hariyani N, Bramantoro T, Nair R, Singh A, Sengupta K. Depression symptoms and recurrent aphthous stomatitis—Evidence from a population-based study in Indonesia. Oral Dis. 2020;26(5):948-954.10.1111/odi.13303.
2. Edgar NR, Saleh D, Miller RA. Recurrent Aphthous Stomatitis: A Review. J. Clin. Aesthet. Dermatol. 2017;10(3):26-36.
3. Novrinda H, Azhara CS, Rahardjo A, Ramadhani A, Dong-Hun H. Determinants and inequality of recurrent aphthous stomatitis in an Indonesian population: A cross-sectional study. BMC Oral Health. 2023;23(1024):1-7.https://doi.org/10.1186/s12903-023-03683-8.
4. Milia E, Sotgiu MA, Spano G, Filigheddu E, Gallusi G, Campanella V. Recurrent aphthous stomatitis (RAS): Guideline for differential diagnosis and management. Eur. J. Paediatr. Dent. 2022;23(1):73-78.10.23804/ejpd.2022.23.01.14.
5. Manfredini M, Guida S, Giovani M, Lippolis N, Spinas E, Farnetani F, Dattola A, Matteo ED, Pellacani G, Giannetti L. Recurrent aphthous stomatitis: Treatment and management. Dermatol. Pract. Concept. 2021;11(4):e2021099. https://doi.org/10.5826/dpc.1104a99.
6. Liu JX, Werner J, Kirsch T, Zuckerman JD, Virk MS. Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts. J. Bone. Jt. Infect. 2018;3(4):165-172.
7. Mimura MA, Hirota SK, Sugaya NN, Migliari DA. Systemic treatment in severe cases of recurrent aphthous stomatitis: An open trial. Clinics (Sao Paulo, Brazil). 2009;64(3):193-198.https://doi.org/10.1590/S1807-59322009000300008.
8. Casale M, Moffa A, Vella P, Rinaldi V, Lopez MA, Grimaldi V, Salvinelli S. Systematic review: The efficacy of topical hyaluronic acid on oral ulcers. J. Biol. Regul. Homeost. Agents. 2017;31:63-69.
9. Pambayun R, Utami DP, Santoso B, Widowati TW, Dewi SRP. Antiseptic effect of betel quid extract on lip mucosal wound of male Wistar (Rattus novergicus) rats. J. Int. Dent. Med. Res. 2018;11(2):621-627.
10. Pratiwi AR, Herawati E, Nur’aeny N. Comparison of anti-inflammatory efficacy of curcumin in Curcuma longa L. with triamcinolone acetonide for minor recurrent aphthous stomatitis: A systematic review. J. Int. Dent. Med. Res. 2022;15(3):1359-1365.
11. Al-Mamoori F, Al-Tawalbe DM, Alnaqeeb M. Medicinal plants for the treatment and management of oral infections: A review. Trop. J. Nat. Prod. Res. 2021; 5(9):1528-1536.
12. Bustamante-Pesantes KE, Miranda-Martínez M, Gutiérrez-Gaitén YI, Guaranda IAC, Pesantes-Dominguez O, Fernández MC. Chemical composition, acute oral toxicity, and analgesic activity of hydroalcoholic extracts of Mimusops coriacea (A.DC) Miq (Sapotaceae). Trop. J. Nat. Prod. Res. 2023;7(4):2688-2695.http://www.doi.org/10.26538/tjnpr/v7i4.3.
13. Okolie NP, Falodun A, Davids O. Evaluation of the antioxidant activity of root extract of pepper fruit (Dennetia tripetala), and its potential for the inhibition of lipid peroxidation. Afr. J. Tradit. Complement. Altern. Med. 2014 11(3):221-227.10.4314/ ajtcam.v11i3.31.
14. Yi S, Zou L, Li Z, Sakao K, Wang Y, Hou X. In vitro antioxidant activity of areca nut polyphenol extracts on RAW264.7 Cells. Foods 2022;11(22):3607. https://doi.org/10.3390/foods112236 07.
15. Rangani SC, Marapana RAUJ, Senanayake GSA, Perera PRD, Pathmalal MM, Amarasinghe HK. Correlation analysis of phenolic compounds, antioxidant potential, oxygen radical scavenging capacity, and alkaloid content in ripe and unripe Areca catechu from major cultivation areas in Sri Lanka. Int. Food Res. 2023;3(2):100361.https://doi.org/10.1016/ j.afres.2023.100361.
16. Kumar AA, Abuthahir SSS, Aboul-Enein HY. Phytochemical extraction and comparative analysis of antioxidant activities of Areca catechu L. nut extracts. Pharmacia. 2022;69(2):447-451.https://doi.org/10.3897/pharmacia.69.e77829.
17. Jam N, Hajimohammadi R, Gharbani P, Mehrizad A. Evaluation of antibacterial activity of aqueous, ethanolic, and methanolic extracts of areca nut fruit on selected bacteria. Biomed Res. Int. 2021; Apr (2021):6663399.https://doi.org/10.1155/2021/66633 99.
18. Byun NY, Heo MR, Yim SH. Correlation of anti-wrinkling and free radical antioxidant activities of areca nut with phenolic and flavonoid contents. Food Sci. Technol. 2021;41(4):1041-1049.https://doi.org/10.1590/fst.35520
19. Bhandare AM, Kshirsagar AD, Vyawahare NS, Hadambar AA, Thorve VS. Potential analgesic, anti-inflammatory, and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut. Food Chem. Toxicol. 2010;48(12):3412-3417.10.1016/ j.fct.2010.09.013.
20. Yamson ECP, Tubalinal AS, Viloria VV, Mingala CN. Anthelmintic effect of betel nut (Areca catechu) and neem (Azadirachta indica) extract against liver fluke (Fasciola spp). J. Adv. Vet. Anim. Res. 2019;6(1):44-49. https://doi.org/10.5455/ javar.2019.e310.
21. Khan S, Mehmood MH, Ali ANA, Ahmed FS, Dar A, Gilani A. Studies on anti-inflammatory and analgesic activities of betel nut in rodents. J. Ethnopharmacol. 2011;135(3):654-661. https://doi.org/10.1016/j.jep.2011.03.064.
22. Sari LM, Wulandari D, Bustami A, Subita GP, Auerkari EA. Tannin screening, phenolic compounds analysis, and antiproliferative activity of areca nut extract by decreasing Ki-67 protein in oral squamous carcinoma cell lines. Trop. J. Nat. Prod. Res. 2020;4(9):563-570.
23. Wei L, Hung S, Lu H, Batzorig U, Huang Y, Chang J. Areca nut extract (ANE) inhibits the progression of hepatocellular carcinoma cells via activation of ROS production and activation of autophagy. Int. J. Med. Sci. 2021;18(15):3452-3462.https://doi.org/10.7150/ijms.61570.
24. Seyyedi A, Sanatkhani M, Pakfetrat A, Olyaee P. The therapeutic effects of chamomilla tincture mouthwash on oral aphthae: A randomized clinical trial. J. Clin. Exp. Dent. 2014;6(5):e535-e538.https://doi.org/10.4317/jced.51472.
25. Babaee N, Zabihi E, Mohseni S, Moghadamnia AA. Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent aphthous stomatitis. Dent. Res. J. 2012;9(4):381-385.
26. Milanda T, Abdelwahab Mohammed AF, Elamin KM, Wilar G, Suharyani I, Wathoni N. Alginate/chitosan-based hydrogel film containing α-mangostin for recurrent aphthous stomatitis therapy in rats. Pharmaceutics. 2022;14(8):1709. https://doi.org/10.3390/ pharmaceutics14081709.
27. Mundial A. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. J. Am. Med. Assoc. 2013;310(20):2191–2194.10.1001/ jama.2013.281053.
28. Dalessandri D, Zotti F, Laffranchi L, Migliorati M, Isola G, Bonetti S, Visconti L. 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. 2019;19(1):153. https://doi.org/10.1186/s12903-019-0850-1.
29. Hadian Z, Moghadamnia AA, Kazemi S, Shirzad A. Effect of omega-3 on recurrent aphthous stomatitis and improvement of quality of life. Int. J. Dent. 2021 10(2021):6617575. https://doi.org/10.1155/2021/6617575.
30. Rivera C, Muñoz-Pastén M, Núñez-Muñoz E, Hernández-Olivos R. Recurrent aphthous stomatitis affects quality of life. A case-control study. Clin. Cosmet. Investig. Dent. 2022;14:217-223. https://doi.org/10.2147/CCIDE.S369481.
31. Chiang C, Yu-Fong Chang J, Wang Y, Wu Y, Wu Y, Sun A. Recurrent aphthous stomatitis – Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management. J. Formos. Med. Assoc. 2019;118(9):1279-1289.https://doi.org/10.1016/ j.jfma.2018.10.023.
32. Katebi K, Asr SY, Mahboobi Z, Faramarzi E, Sharififard N Recurrent aphthous stomatitis (RAS) and its related factors among the Azar cohort population. BMC Oral Health. 2025;25(596):1-8.https://doi.org/10.1186/s12903-025-05981-9.
33. Seo HR, Chung KB, Kim D-Y. The possible impact of zinc-enriched multivitamins on treatment-naïve recurrent aphthous stomatitis patients. J. Clin. Med. 2025;14(1):260.https://doi.org/ 10.3390/jcm14010260.
34. Sandhiutami NMD, Fahleni F, Miftahurrohmah N, Widhiyasari NKA, Azalia A, Amalia I. Enhanced wound healing effect of Areca catechu L. ointment via antibacterial activity and anti-inflammatory process at grade IIA burns in rats. J. Herbmed. Pharmacol. 2023;12(3):388-398.10.34172/jhp.2023.42.
35. Liu P, Chang Y. The controversial roles of areca nut: Medicine or toxin? Int. J. Mol. Sci. 2022;24(10):8996.https://doi.org/ 10.3390/ijms24108996.
36. Pithayanukul P, Nithitanakool S, Bavovada R. Hepatoprotective potential of extracts from seeds of Areca catechu and nutgalls of Quercus infectoria. Molecules. 2009 14(12):4987-5000.10.3390/molecules14124987.
37. Johnstone WM, Honeycutt JL, Deck CA, Borski RJ. Nongenomic glucocorticoid effects and their mechanisms of action in vertebrates. Int. Rev. Cell. Mol. Biol. 2019;346:51-96.
38. Abraham A, Roga G. Topical steroid-damaged skin. Indian J. Dermatol. 2014;59(5):456-459.
39. Cole TJ, Short KL, Hooper SB. The science of steroids. Semin. Fetal. Neonatal. Med. 2019;24(3):170-175.
40. Dubashynskaya NV, Petrova VA, Skorik YA Biopolymer drug delivery systems for oromucosal application: recent trends in pharmaceutical R&D. J. Mol. Sci. 2024;25(10):1-20.https://doi.org/10.3390/ijms25105359.
41. Zhao L, Li Y, Yang S, Zhang P, Wang J. Anti-nociceptive effect of total alkaloids isolated from the seeds of Areca catechu L (Arecaceae) in mice. Trop. J. Pharm. Res. 2017;16:363-369.
42. Cai M, Yang Z, Huang X, Li J, Bao W, Cui JW, Ma LQ, Tong HY. Mongolian medicine areca thirteen pill (GY-13) improved depressive syndrome via upregulating cAMP/PKA /CREB/BDNF signaling pathway. J. Ethnopharm acol. 2022;15(293):115310.
43. Varela ML, Mogildea M, Moreno I, Lopes A. Acute inflammation and metabolism. Inflamm. 2018;41(4):1115-1127.10.1007/s10753-018-0739-1.


