Efficacy of Glycyrrhiza glabra in the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Randomized Controlled Trials
Abstract
1. Introduction
2. Methods
2.1. Study Protocols
2.2. Inclusion and Exclusion Criteria
- Type of study: randomized controlled/clinical trial (RCT) and double-blind clinical trial study evaluating the topical treatment of Glycyrrhiza glabra in RAS;
- Type of participant (P): patient with RAS lesion (minor, major, or herpetiform type) diagnosed from the subjective and clinical assessments;
- Type of intervention (I): treatment using Glycyrrhiza glabra in any dosage form, frequency, and duration of treatment;
- Type of comparator (C): control group treated with placebo, antiseptic, or anti-inflammatory agent;
- Type of outcome measure (O): pain intensity measured with a visual analog scale (VAS), the reduction in ulcerated lesion diameter, and the period of RAS healing.
- Non-RCTs, reviews, animal studies, and in vitro studies;
- Patients with underlying diseases, like diabetes mellitus and autoimmune and allergy diseases;
- The clinical diagnosis of RAS is not defined;
- Articles not published in English language.
2.3. Search Strategies
- “licorice” or “Glycyrrhiza glabra”, AND;
- “Recurrent aphthous stomatitis” OR “recurrent aphthous ulceration” OR “RAS” OR “aphthous ulcer” OR “oral ulcer” OR “oral wound” OR “oral lesion”.
2.4. Study Selection and Data Extraction
2.5. Critical Appraisal for Quality if the Study
3. Results
3.1. Study Selection
3.2. Characteristics of the Study
3.3. Glycyrrhiza glabra Alleviated RAS-Related Pain Intensity
3.4. Glycyrrhiza glabra Accelerating Reduction in RAS Diameter
3.5. Glycyrrhiza glabra Effect on RAS-Related Ulcer Healing Time
3.6. Quality of the Study
4. Discussion
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Type of Study | Type of RAS | Control Group | Intervention Group | Reference | |||
---|---|---|---|---|---|---|---|
Subject (n) | Dosage From | Subject (n) | Dosage Form | Frequency of Treatment | |||
Placebo-controlled, observer-blind, consecutive-group clinical trial | Minor | - | Vehicle patch | 15 | Patch | Once daily | [23] |
Randomized controlled trial | Minor | 7 | No treatment | 7 | Paste | Three times daily | [24] |
Randomized controlled trial | NS | 10 | No treatment | 10 | Paste | Four times daily | [25] |
Randomized controlled double-blind | Minor | 20 | Placebo patch | 20 | Paste | Four times daily | [26] |
20 | Diphenhydramine mouthwash | ||||||
Randomized double-blind, placebo-controlled trial | Minor Major Herpetiform | 24 | Xylitol mouthwash | 30 | Mouthwash | Four times daily | [27] |
Double-blind clinical trial | Minor | 21 | Placebo mucoadhesive tablet | 21 | Mucoadhesive tablet | Three times daily | [28] |
Double-blind clinical trial | NR | 23 | Placebo patch | 23 | Patch | Once daily | [29] |
23 | No treatment |
Glycyrrhiza glabra | Processing Technique | Dosage Form | Concentration | Reference |
---|---|---|---|---|
NR | Maceration | Patch | 1% | [23] |
Roots and rhizomes | Maceration | Paste | Whole extract | [24] |
Roots | Maceration | Paste | 1% | [25] |
Roots and rhizomes | Maceration | Paste | 5% | [26] |
NR | NR | Mouthwash | NR | [27] |
Roots | Maceration | Mucoadhesive tablet | 17.25% | [28] |
Roots | NR | Patch | NR | [29] |
Dosage form of Glycyrrhiza glabra | Control | Duration of Treatment | Pain Assessment | Result | Reference |
---|---|---|---|---|---|
Patch | Vehicle patch | Once daily | VAS | Significant pain reduction after 1 and 5 days | [23] |
Paste | No treatment | Four times daily | VAS | Significant pain reduction after 2 and 5 days | [25] |
Paste | Placebo paste | Four times daily | VAS | Significant pain reduction after 3 and 5 days | [26] |
Mouthwash | Xylitol mouthwash | Four times daily | VAS | Significant pain reduction after 1 and 2 days | [27] |
Mucoadhesive tablet | Diphenhydramine mouthwash | Three times daily | VAS | Significant pain reduction after 1 until 7 days | [28] |
Placebo mucoadhesive tablet | |||||
Patch | Placebo or patch | Once daily | VAS | Significant pain reduction after 1 day | [29] |
No treatment |
Dosage form of Glycyrrhiza glabra | Control | Duration of Treatment | Result | Reference |
---|---|---|---|---|
Patch | Vehicle patch | Once daily | Significant ulcer diameter reduction after 5 days | [23] |
Paste | No treatment | Three times daily | Significant ulcer diameter reduction after 2 and 3 days | [24] |
Paste | No treatment | Four times daily | Significant ulcer diameter reduction after 2 and 5 days | [25] |
Paste | Placebo paste | Four times daily | Significant ulcer diameter reduction after 3 and 5 days | [26] |
Diphenhydramine mouthwash | ||||
Mouthwash | Xylitol mouthwash | Four times daily | Significant ulcer diameter reduction after 1 and 2 days | [27] |
Mucoadhesive tablet | Placebo mucoadhesive tablet | Three times daily | Significant ulcer diameter reduction after 3, 5, and 7 days | [28] |
Patch | Placebo or no treatment | Once daily | Significant ulcer diameter reduction after 8 days | [29] |
Dosage form of Glycyrrhiza glabra | Control | Duration of Treatment | Result | Reference |
---|---|---|---|---|
Patch | Vehicle patch | Once a day | No significant healing time | [23] |
Paste | Placebo paste | Four times daily | Significantly faster ulcer healing | [26] |
Diphenhydramine mouthwash | ||||
Mouthwash | Diphenhydramine mouthwash | Four times daily | Significantly faster ulcer healing after 1, 3, and 7 days | [29] |
Assessment Criteria | [23] | [24] | [26] | [28] | [29] | [27] | [25] |
---|---|---|---|---|---|---|---|
Selection criteria | √ | √ | √ | √ | √ | √ | √ |
Randomization | x | X | √ | o | o | o | o |
Blinding | o | X | √ | o | x | √ | X |
Follow-up rate | X | X | X | X | X | √ | X |
Intervention detail | √ | √ | √ | √ | √ | √ | √ |
Outcome measure | √ | √ | √ | √ | √ | √ | √ |
Statistical analysis | √ | √ | √ | √ | √ | √ | √ |
Quality | Moderate | Moderate | High | Moderate | Moderate | High | Moderate |
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© 2025 by the authors. Published by MDPI on behalf of the Oman Medical Association. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Iskandar, A.S.; Nisa, G.S.N.; Queen, H.; Wicaksono, S.; Surboyo, M.D.C.; Ernawati, D.S. Efficacy of Glycyrrhiza glabra in the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Randomized Controlled Trials. J. Oman Med. Assoc. 2025, 2, 8. https://doi.org/10.3390/joma2010008
Iskandar AS, Nisa GSN, Queen H, Wicaksono S, Surboyo MDC, Ernawati DS. Efficacy of Glycyrrhiza glabra in the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Randomized Controlled Trials. Journal of the Oman Medical Association. 2025; 2(1):8. https://doi.org/10.3390/joma2010008
Chicago/Turabian StyleIskandar, Annisa Sabrina, Ghinaya Shaliha Nursaida Nisa, Hanifa Queen, Satutya Wicaksono, Meircurius Dwi Condro Surboyo, and Diah Savitri Ernawati. 2025. "Efficacy of Glycyrrhiza glabra in the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Randomized Controlled Trials" Journal of the Oman Medical Association 2, no. 1: 8. https://doi.org/10.3390/joma2010008
APA StyleIskandar, A. S., Nisa, G. S. N., Queen, H., Wicaksono, S., Surboyo, M. D. C., & Ernawati, D. S. (2025). Efficacy of Glycyrrhiza glabra in the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Randomized Controlled Trials. Journal of the Oman Medical Association, 2(1), 8. https://doi.org/10.3390/joma2010008