# Effects of glycyrrhizin on healing and prevention of recurrent aphthous stomatitis in hamster models

## TL;DR

This study shows that low concentrations of glycyrrhizin can help heal and prevent mouth sores in hamsters, suggesting it could be useful for treating recurring mouth ulcers in humans.

## Contribution

The study introduces a novel evaluation of glycyrrhizin's therapeutic and preventive effects on RAS using hamster models and identifies optimal low concentrations.

## Key findings

- Low concentrations of glycyrrhizin (0.0065%) improved healing and reduced inflammation in hamster models of stomatitis.
- High concentrations of glycyrrhizin (0.33%) were less effective and even increased inflammation in some cases.
- Low glycyrrhizin concentrations suppressed PGE₂ expression in human oral keratinocytes, supporting its anti-inflammatory role.

## Abstract

Recurrent aphthous stomatitis (RAS), a major type of stomatitis, can significantly impair quality of life. The therapeutic and preventive effects of glycyrrhizin (GL), a compound known for its anti-inflammatory properties, remain unclear due to the lack of appropriate animal models, especially for prevention studies. Therefore, this study aimed to evaluate the therapeutic and preventive effects of GL and determine the optimal concentrations using two hamster models (stomatitis-initiation model and stomatitis-healing model) representing the initiation and healing phases of RAS. The effects were evaluated through macroscopic and histological analyses, gene expression profiling in hamster buccal tissues, and prostaglandin E2 (PGE2) assays in lipopolysaccharide-stimulated human oral keratinocytes. In the stomatitis-healing model, a low concentration of GL (0.0065%) significantly increased the cure rate and histologically reduced the numbers of vessels and lymphocytes. In the stomatitis-initiation model, low concentrations of GL (0.0065% and 0.033%) significantly decreased the edema score and histologically reduced the numbers of vessels and neutrophils, as well as the mRNA expression levels of interleukin-6 and cyclooxygenase-2. In contrast, a high concentration of GL (0.33%) showed inferior efficacy compared with low concentrations in both models. Similarly, in LPS-stimulated human oral keratinocytes, low GL concentrations suppressed PGE₂ protein expression, while the highest concentration increased it. These findings show that GL promotes healing and prevents the onset of stomatitis at specific concentrations, underscoring the importance of optimal dosing and supporting the potential clinical application of GL in the management of RAS.