Topical Licorice for Aphthous: A Systematic Review of Clinical Trials

Background: Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease that affects oral mucosa. The coating agents, topical analgesics, and topical steroids are usually used as treatment methods. Glycyrrhiza glabra has been used for RAS treatment based on its anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, a systemic review on the therapeutic effect of topical licorice on RAS management was performed. Methods: Science Direct, Scopus, Cochrane databases, PubMed Google Scholar, and ResearchGate were searched up to September 2021 to find all English randomized clinical trials studying the effect of G. glabra, or its compositions on RAS. Meta-analysis was not conducted because of data heterogeneity. Articles were reviewed qualitatively, and only those with a Jadad score ≥3 were included. Animal studies, in vitro, review papers, non-English papers, and case reports were excluded.Results: Six studies with 314 subjects were included after screening. The result showed licorice has significant effects on RAS pain reduction, ulcer size, and healing time. Its effectiveness is related to its dose-dependent anti-inflammatory and antioxidant effects through several mechanisms. It also has antibacterial effects against Streptococci mutans and Porphyromonas gingivalis as another mechanism of action in RAS treatment. In addition, licorice can elevate the epidermal growth factor (EGF) level compared to the control group, which has an essential role in oral mucosal tissue integrity. Conclusion: Licorice extract has been used in different dosage forms, including paste, patch, and mouthwash with concentrations of 1% or 5%. The healing time after licorice therapy is expected to be within 4-8 days. Licorice did not show any adverse effect in the intervention groups, indicating its effectiveness and safety in RAS treatment.