Escin, a naturally derived material isolated from horse chestnut, is used as an anti-inflammatory and anti-edema agent. This study aimed to evaluate its effects on lymphedema in a rat tail model. We divided the rats into five groups. The treatment groups received topical application of escin gel at concentrations of 20%, 10%, 2%, and 0.5% for 4 weeks. The fifth group served as a control. We performed volumetric (water displacement) tests, H&E staining, and LYVE-1 immunohistochemical staining, followed by statistical evaluation. All treatment groups showed significant volumetric reductions compared with the control group, but no significant differences were observed between the treatment groups. H&E staining showed a significant reduction in dermal thickness in the 20%, 10%, and 2% escin treatment groups compared to the control group. Within the treatment groups, the 2% escin group showed a significant difference compared with the 20% and 10% escin groups (p = 0.021 for both). LYVE-1 immunohistochemical staining revealed a significantly higher mean lymphatic vessel count in the 2% escin group compared with the 20%, 10%, and 0.5% escin-treated groups and the control group (p = 0.019, p = 0.025, p = 0.019, and p = 0.032 respectively). Topical escin applied to a rat tail model of acute lymphedema resulted in a significant reduction in tail volume, reduced dermal thickness, and increased lymphatic structures. The 2% escin concentration may be the optimal dose for improving lymphedema in this model. Further research is warranted to explore the clinical application of escin in patients with lymphedema.
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