Author(s):
Vaishali Kilor, Nidhi Sapkal, Sana Shaikh
Email(s):
v_kilor@yahoo.com
DOI:
10.52711/0974-360X.2025.00209 
Address:
Vaishali Kilor*, Nidhi Sapkal, Sana Shaikh
Gurunanak College of Pharmacy, Kashi Nagar, Near Dixit Nagar, Nari Road, Nagpur, MS, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 3,
Year - 2025
ABSTRACT:
Recurrent aphthous stomatitis (RAS) is the repeated occurrence of lesions in the intraoral sites having diverse etiology leading to pain, inflammation, and difficulty in eating and speaking. Common treatment options available for RAS are analgesics, corticosteroids, local anesthetics, and antimicrobial agents. The purpose is to reduce the intensity of pain, inflammation, and duration of the ulcer. All the above-mentioned medications if used for a longer duration may result in several complications including antibiotic resistance. It is commonly observed that patients suffering from RAS initiate self-treatment like the application of honey, and turmeric to ulcers, chewing of guava leaves, beetle leaves, etc., based on traditional knowledge which results in inconsistent relief and ultimately treatment shifts towards the use of corticosteroids, analgesic as well as antibiotics. There is a need for evidence-based systematic studies that lead to the availability of formulations containing herbal medicines for guaranteed quick relief from pain and reducing recurrence of mouth ulcers. Thus, to prove efficacy of traditional herbal medicine, several clinical trials are being done where these medicines are used as single extract for topical application. The present study aims to critically assess the available data of clinical trials on the topical treatment of RAS using plant-based medicines and identify the most promising plant-based medicine that gives quick relief from RAS.
Cite this article:
Vaishali Kilor, Nidhi Sapkal, Sana Shaikh. Review of clinical studies of herbal products as a treatment option in recurrent Aphthous stomatitis. Research Journal of Pharmacy and Technology. 2025;18(3):1456-5. doi: 10.52711/0974-360X.2025.00209
Cite(Electronic):
Vaishali Kilor, Nidhi Sapkal, Sana Shaikh. Review of clinical studies of herbal products as a treatment option in recurrent Aphthous stomatitis. Research Journal of Pharmacy and Technology. 2025;18(3):1456-5. doi: 10.52711/0974-360X.2025.00209 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-3-70
REFERENCES:
1. Liu, Y.; He, M.; Yin, T.; Zheng, Z.; Fang, C.; Peng, S. Prevalence of Recurrent Aphthous Stomatitis, Oral Submucosal Fibrosis and Oral Leukoplakia in Doctor/Nurse and Police Officer Population. BMC Oral Health. 2022: 22(1); 353. https://doi.org/10.1186/s12903-022-02382-0.
2. Edgar, N. R.; Saleh, D.; Miller, R. A. Recurrent Aphthous Stomatitis: A Review. J. Clin. Aesthetic Dermatol. 2017; 10(3): 26–36.
3. Altenburg, A.; Abdel-Naser, M. B.; Seeber, H.; Abdallah, M.; Zouboulis, C. C. Practical Aspects of Management of Recurrent Aphthous Stomatitis. J. Eur. Acad. Dermatol. Venereol. JEADV. 2007: 21(8): 1019–1026. https://doi.org/10.1111/j.1468-3083.2007.02393.x.
4. Scully, C. ABC of Oral Health: Mouth Ulcers and Other Causes of Orofacial Soreness and Pain. BMJ. 2000; 321(7254): 162–165. https://doi.org/10.1136/bmj.321.7254.162.
5. Wu, Y.H.; Wu, Y.C.; Lang, M.J.; Lee, Y.P.; Jin, Y.T.; Chiang, C.P. Review of Oral Ulcerative Lesions in COVID-19 Patients: A Comprehensive Study of 51 Cases. J. Dent. Sci. 2021; 16(4): 1066–1073. https://doi.org/10.1016/j.jds.2021.07.001.
6. Tarakji, B.; Gazal, G.; Al-Maweri, S. A.; Azzeghaiby, S. N.; Alaizari, N. Guideline for the Diagnosis and Treatment of Recurrent Aphthous Stomatitis for Dental Practitioners. J. Int. Oral Health JIOH. 2015; 7(5): 74–80.
7. Chen, H.; Sui, Q.; Chen, Y.; Ge, L.; Lin, M. Impact of Haematologic Deficiencies on Recurrent Aphthous Ulceration: A Meta-Analysis. Br. Dent. J. 2015; 218(4): E8–E8. https://doi.org/10.1038/sj.bdj.2015.100.
8. Sharma, R.; Pallagatti, S.; Aggarwal, A.; Sheikh, S.; Singh, R.; Gupta, D. A Randomized, Double-Blind, Placebo-Controlled Trial on Clinical Efficacy of Topical Agents in Reducing Pain and Frequency of Recurrent Aphthous Ulcers. Open Dent. J. 2018; 12(1): 700–713. https://doi.org/10.2174/1745017901814010700.
9. Shahare, N.; Chouhan, S.; Darwhekar, G. N. Herbs Used in Treatment of Mouth Ulcer- a Review: Herbal Medicines for Treatment of Mouth Ulcer. Int. J. Pharmacogn. Chem. 2021: 68–74. https://doi.org/10.46796/ijpc.v2i3.212.
10. Babaee, N.; Mansourian, A.; Momen-Heravi, F.; Moghadamnia, A.; Momen-Beitollahi, J. The Efficacy of a Paste Containing Myrtus Communis (Myrtle) in the Management of Recurrent Aphthous Stomatitis: A Randomized Controlled Trial. Clin. Oral Investig. 2010; 14(1): 65–70. https://doi.org/10.1007/s00784-009-0267-3.
11. Shahin-Jafari; Hassan-Farsam; Massoud-Amanlou; Katayoun-Borhan-mojabi. Comparartive Study of Zataria Multiflora and Anthemis Nobelis Extracts with Myrthus Communis Preparation in The Treatment of Recurrent Aphthous Stomatitis. DARU J. Pharm. Sci. 2003; 11(1): 23–27.
12. Giampieri, F.; Cianciosi, D.; Forbes‐Hernández, T. Y. Myrtle (Myrtus Communis L.) Berries, Seeds, Leaves, and Essential Oils: New Undiscovered Sources of Natural Compounds with Promising Health Benefits. Food Front. 2020; 1(3): 276–295. https://doi.org/10.1002/fft2.37.
13. Andishe Tadbir, A.; Pourshahidi, S.; Ebrahimi, H.; Hajipour, Z.; Memarzade, M. R.; Shirazian, S. The Effect of Matricaria Chamomilla (Chamomile) Extract in Orabase on Minor Aphthous Stomatitis, a Randomized Clinical Trial. J. Herb. Med. 2015; 5(2): 71–76. https://doi.org/10.1016/j.hermed.2015.05.001.
14. Guintu, D. F. Z. Effectivity of Guava Leaves (Psidium Guajava) as Mouthwash for Patients with Aphthous Ulcers. Head Neck Surg. 2013; 28(2).
15. Nayak, N.; Varghese, J.; Shetty, S.; Bhat, V.; Durgekar, T.; Lobo, R.; Nayak, U. Y.; U, V. Evaluation of a Mouthrinse Containing Guava Leaf Extract as Part of Comprehensive Oral Care Regimen- a Randomized Placebo-Controlled Clinical Trial. BMC Complement. Altern. Med. 2019; 19: 327. https://doi.org/10.1186/s12906-019-2745-8.
16. Rezig, L.; Chouaibi, M.; Msaada, K.; Hamdi, S. Chemical Composition and Profile Characterisation of Pumpkin (Cucurbita Maxima) Seed Oil. Ind. Crops Prod. 2012; 37(1): 82–87. https://doi.org/10.1016/j.indcrop.2011.12.004.
17. Batool, M.; Ranjha, M. M. A. N.; Roobab, U.; Manzoor, M. F.; Farooq, U.; Nadeem, H. R.; Nadeem, M.; Kanwal, R.; AbdElgawad, H.; Jaouni, S. K. A.; et al. Nutritional Value, Phytochemical Potential, and Therapeutic Benefits of Pumpkin (Cucurbita Sp.). Plants. 2022; 11(11). https://doi.org/10.3390/plants11111394.
18. Sharquie, K. E.; Noaimi, A. A.; Latif, T. M. Treatment of Recurrent Aphthous Stomatitis by 100% Topical Pumpkin Seed Oil. J. Cosmet. Dermatol. Sci. Appl. 2017; 7(4): 324–335. https://doi.org/10.4236/jcdsa.2017.74029.
19. Manifar, S.; Obwaller, A.; Gharehgozloo, A.; Kordi, H. B. S.; Akhondzadeh, S. Curcumin Gel in the Treatment of Minor Aphthous Ulcer: A Randomized, Placebo- Controlled Trial. 2012; 11(41).
20. Halim, Daddy; Khalik, Nor; Taib, Haslina; Pohchi, Abdullah; Hassan, Akram; Alam, Mohammad. Novel Material in the Treatment of Minor Oral Recurrent Aphthous Stomatitis. Int. Med. J. 2013; 20(3): 392–394.
21. Pandharipande, R.; Chandak, R.; Sathawane, R.; Lanjekar, A.; Gaikwad, R.; Khandelwal, V.; Kurawar, K. To Evaluate Efficiency of Curcumin and Honey in Patients with Recurrent Aphthous Stomatitis: A Randomized Clinical Controlled Trial. 2019; 12.
22. Suzan M. Abdul Raheem. Evaluate the Efficiency of Sage (Salvia Officinalis) and Curcumin Mouthwash in the Treatment of Recurrent Aphthous Stomatitis (Comparative Study). J. Al Rafidain Univ. Coll. 2021; 48: 224–232.
23. Fiore, C.; Eisenhut, M.; Ragazzi, E.; Zanchin, G.; Armanini, D. A History of the Therapeutic Use of Liquorice in Europe. J. Ethnopharmacol. 2005; 99(3): 317–324. https://doi.org/10.1016/j.jep.2005.04.015.
24. Hassan, K. A. M.; Khalil, S. Original Research Article. 2013; 4(3).
25. Galal Maha; Ammar N. M.; Mostafa Dina; Nastry Sherine. Therapeutic Efficacy of Herbal Formulations for Recurrent Aphthous Ulcer. Correlation with Salivary Epidermal Growth Factor. Life Sci. J. 2012; 9: 2398–2406.
26. Nasry, S. A.; El Shenawy, H. M.; Mostafa, D.; Ammar, N. M. Different Modalities for Treatment of Recurrent Aphthous Stomatitis. A Randomized Clinical Trial. J. Clin. Exp. Dent. 2016; 8 (5): e517–e522. https://doi.org/10.4317/jced.52877.
27. Moghadamnia, A. A.; Motallebnejad, M.; Khanian, M. The Efficacy of the Bioadhesive Patches Containing Licorice Extract in the Management of Recurrent Aphthous Stomatitis. Phytother. Res. PTR. 2009; 23(2): 246–250. https://doi.org/10.1002/ptr.2601.
28. Surjushe, A.; Vasani, R.; Saple, D. G. Aloe vera: A short review. Indian J. Dermatol. 2008; 53(4): 163–166. https://doi.org/10.4103/0019-5154.44785.
29. Babaee, N.; Zabihi, E.; Mohseni, S.; Moghadamnia, A. A. Evaluation of the Therapeutic Effects of Aloe Vera Gel on Minor Recurrent Aphthous Stomatitis. Dent. Res. J. 2012; 9(4).
30. Mansour, G.; Ouda, S.; Shaker, A.; Abdallah, H. M. Clinical Efficacy of New Aloe Vera- and Myrrh-Based Oral Mucoadhesive Gels in the Management of Minor Recurrent Aphthous Stomatitis: A Randomized, Double-Blind, Vehicle-Controlled Study. J. Oral Pathol. Med. Off. Publ. Int. Assoc. Oral Pathol. Am. Acad. Oral Pathol., 2014; 43(6): 405–409. https://doi.org/10.1111/jop.12130.
31. Shi, Y.; Wei, K.; Lu, J.; Wei, J.; Hu, X.; Chen, T. A Clinic Trial Evaluating the Effects of Aloe Vera Fermentation Gel on Recurrent Aphthous Stomatitis. Can. J. Infect. Dis. Med. Microbiol., 2020; 2020: e8867548. https://doi.org/10.1155/2020/8867548.
32. Mahboub, M.; Aghazadeh Attari, A. M.; Sheikhalipour, Z.; Mirza Aghazadeh Attari, M.; Davami, B.; Amidfar, A.; Lotfi, M. A Comparative Study of the Impacts of Aloe Vera Gel and Silver Sulfadiazine Cream 1% on Healing, Itching and Pain of Burn Wounds: A Randomized Clinical Trial. J. Caring Sci. 2021; 11(3): 132–138. https://doi.org/10.34172/jcs.2021.036.
33. Khorasani, G.; Hosseinimehr, S. J.; Azadbakht, M.; Zamani, A.; Mahdavi, M. R. Aloe versus Silver Sulfadiazine Creams for Second-Degree Burns: A Randomized Controlled Study. Surg. Today. 2009. 39(7): 587–591. https://doi.org/10.1007/s00595-008-3944-y.
34. Armas, E. D.; Sarracent, Y.; Marrero, E.; Fernández, O.; Branford-White, C. Efficacy of Rhizophora Mangle Aqueous Bark Extract (RMABE) in the Treatment of Aphthous Ulcers: A Pilot Study. Curr. Med. Res. Opin. 2005; 21(11): 1711–1715. https://doi.org/10.1185/030079905X65493.
35. Jiang, X.-W.; Zhang, Y.; Zhu, Y.-L.; Zhang, H.; Lu, K.; Li, F.-F.; Peng, H.-Y. Effects of Berberine Gelatin on Recurrent Aphthous Stomatitis: A Randomized, Placebo-Controlled, Double-Blind Trial in a Chinese Cohort. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2013; 115(2): 212–217. https://doi.org/10.1016/j.oooo.2012.09.009.
36. Bechir, A; Sirbu, Rodica; Pacurar, Mariana; Podariu, Angela; Monea, Monica; Bechir, Edwin; Ghergic, Doina. The Effect of Collagenic Gels with Marine Algae Extracts Mixtures in the Treatment of Recurrent Aphthous Stomatitis. Rev. Chim. -Buchar. - Orig. Ed. 2014; 65(3): 362–368.
37. Bechir, A.; Sirbu, R.; Pacurar, M.; Podariu, A. C.; Monea, M.; Bechir, E. S.; Ghergic, D. L. The Effect of Collagenic Gels with Marine Algae Extracts Mixtures in the Treatment of Recurrent Aphthous Stomatitis. Rev Chim. 2014; 3.
38. Halim, D. S.; Mahanani, E. S.; Saini, R.; Omar, M. A Comparison Study on the Effectiveness of Local Honey and Salicylate Gel for Treatment of Minor Recurrent Aphtous Stomatitis.
39. Haghpanah, P.; Moghadamnia, A. A.; Zarghami, A.; Motallebnejad, M. Muco-Bioadhesive Containing Ginger Officinal E Extract in the Management of Recurrent Aphthous Stomatitis: A Randomized Clinical Study. Casp. J. Intern. Med. 2015; 6(1): 3–8.
40. Liu, X.; Guan, X.; Chen, R.; Hua, H.; Liu, Y.; Yan, Z. Repurposing of Yunnan Baiyao as an Alternative Therapy for Minor Recurrent Aphthous Stomatitis. Evid.-Based Complement. Altern. Med. ECAM. 2012: 2012: 284620. https://doi.org/10.1155/2012/284620.
41. Jin, Y.; Lin, X.; Song, L.; Liu, M.; Zhang, Y.; Qi, X.; Zhao, D. The Effect of Pudilan Anti-Inflammatory Oral Liquid on the Treatment of Mild Recurrent Aphthous Ulcers. Evid. Based Complement. Alternat. Med. 2017; 2017: 1–6. https://doi.org/10.1155/2017/6250892.
42. Liu, Z.; Dou, H. Effects of Four Types of Watermelon Frost Combination Medications for the Treatment of Oral Ulcers: A Network Meta-Analysis. J. Healthc. Eng. 2022; 2022: 1–7. https://doi.org/10.1155/2022/2712403.
43. Moghadamnia, A. A.; Motallebnejad, M.; Khanian, M. The Efficacy of the Bioadhesive Patches Containing Licorice Extract in the Management of Recurrent Aphthous Stomatitis. Phytother. Res. PTR. 2009; 23(2): 246–250. https://doi.org/10.1002/ptr.2601.
44. Mathew-Steiner, S. S.; Roy, S.; Sen, C. K. Collagen in Wound Healing. Bioeng. Basel Switz. 2021; 8(5): 63. https://doi.org/10.3390/bioengineering8050063.
45. Martinotti, S.; Ranzato, E. Honey, Wound Repair and Regenerative Medicine. J. Funct. Biomater. 2018; 9(2): 34. https://doi.org/10.3390/jfb9020034.
46. Bhagavathula, N.; Warner, R. L.; DaSilva, M.; McClintock, S. D.; Barron, A.; Aslam, M. N.; Johnson, K. J.; Varani, J. A Combination of Curcumin and Ginger Extract Improves Abrasion Wound Healing in Corticosteroid-Impaired Hairless Rat Skin. Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc. 2009; 17(3): 360–366. https://doi.org/10.1111/j.1524-475X.2009.00483.x.
47. Yao, Q.; Chang, B.T.; Chen, R.; Wei, Y.J.; Gong, Q.J.; Yu, D.; Zhang, Y.; Han, X.; Yang, H.-B.; Tang, S.-J.; et al. Research Advances in Pharmacology, Safety, and Clinical Applications of Yunnan Baiyao, a Traditional Chinese Medicine Formula. Front. Pharmacol. 2021; 12: 773185. https://doi.org/10.3389/fphar.2021.773185.
48. Nem Kumar Jain, Rituparna Roy, Hero Khan Pathan, Aditi Sharma, Shakhi Ghosh, Santosh Kumar. Formulation and Evaluation of Polyherbal Aqueous Gel from Psidium guajava, Piper betel and Glycerrhiza glabra Extract for Mouth Ulcer Treatment. Res. J. Pharmacognosy and Phytochem. 2020; 12(3):145-148.
49. Akansha Bhandarkar, Amit Alexander, Aditi Bhatt, Pankaj Sahu, Palak Agrawal, Tripti Banjare, Swapnil Gupta, Hemlata Sahu, Shradha Devi Diwedi, Siddharth Kumar Sahu, Pooja Yadav, Kailash Sahu, Deeksha Dewangan, Hemlata Thapa, Deepika, Vinay Sagar Verma, Mukesh Sharma, D. K. Tripathi, Ajazuddin. Formulation and Evaluation of Ascorbic acid Lozenges for the treatment of Oral Ulcer. Research J. Pharm. and Tech. 2018; 11(4):1307-1312
50. Indhumathi. S, Siva Kumar. K. A Review on Medicated Chewing Gum and its Role in Mouth Ulcers. Research J. Pharm. and Tech. 2020; 13(1): 481-484.
51. Mythili Srinivasan, Deshmukh Apurva, Wani Manish, Polshettiwar Satish, Pande Varun, Deshpande Maitreyee, Pandit Ashlesha, Tagalpallewar Amol, Baheti Akshay. Development and In-vitro Effectiveness of Tooth-gel containing Herbal Extracts. Research Journal of Pharmacy and Technology. 2023; 16(3): 1283-8.
52. Bhupen Kalita, Malay K. Das, Anil Kumar Sharma. Novel Phytosome Formulations in Making Herbal Extracts More Effective. Research J. Pharm. and Tech. 2013; 6(11): 1295-1301.
53. Jessy Shaji, Twinkle Haresh Vaswani. Effect of Benzydamine Hydrochloride loaded Nanosponge formulations against mouth ulcers in Albino Wistar Rats. Research J. Pharm. and Tech. 2021; 14(2): 986-990.
54. Hima Jose, K. Krishnakumar, Dineshkumar B. Herbal Extracts based Scaffolds for Wound Healing Therapy. Research J. Pharm. and Tech. 2021; 14(3): 1805-1810.
55. P. Manorama, Valmiki Aruna, Gangadhara Angajala, D. Geetha. Identification of Chemical Constituents, Chromatographic profiling of PHE (Poly Herbal Extract) of selected Indian Medicinal Herbs and its Antioxidant activity Evaluation. Research Journal of Pharmacy and Technology. 2022; 15(8): 3611-7.
56. Indhumathi. S, Siva Kumar. K. A Review on Medicated Chewing Gum and its Role in Mouth Ulcers. Research J. Pharm. and Tech. 2020; 13(1): 481-484.
57. Ranjith Anishetty, Satya Swapna, B. Aishwarya, K. Chaitanya Sravanthi. Evaluation of antibacterial activity potential of extracts of Ricinus communis, Zingiber officinalis and Punica granatum in a Polyherbal Extract. Research J. Pharm. and Tech. 2012; 5(11): 1385-1388