| Summary: | The activation of the Wnt/β-catenin signaling pathway plays a key role in the wound-healing process through tissue regeneration. The extract of <i>Euodia daniellii</i> Hemsl. (<i>E. daniellii</i>), a member of the Rutaceae family, activates the Wnt/β-catenin signaling pathway. However, the function of <i>E. daniellii</i> in wound healing has not yet been elucidated. We performed a migration assay to determine the wound-healing effect of <i>E. daniellii</i> extract in vitro using human keratinocytes and dermal fibroblast. In addition, a mouse acute wound model was used to investigate the cutaneous wound-healing effect of <i>E. daniellii</i> extract in vivo and confirm the potential mechanism. <i>E. daniellii</i> extract enhanced the migration of human keratinocytes and dermal fibroblasts via the activation of the Wnt/β-catenin pathway. Moreover, the <i>E. daniellii</i> extract increased the levels of keratin 14, PCNA, collagen I, and α-SMA, with nuclei accumulation of β-catenin in vitro. <i>E. daniellii</i> extract also efficiently accelerated re-epithelialization and stimulated wound healing in vivo. Furthermore, we confirmed that hesperidin, one of the components of <i>E. daniellii</i>, efficiently accelerated the migration of human keratinocytes and dermal fibroblasts, as well as wound healing in vivo via the activation of the Wnt/β-catenin pathway. Overall, <i>E. daniellii</i> extract and its active component, hesperidin, have potential to be used as therapeutic agents for wound healing.
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