Esculin promotes skin wound healing in mice and regulates the Wnt/β-catenin signaling pathway.

OBJECTIVE: Previous studies reported that esculin could protect against renal ischemia-reperfusion injury and liver injury, but its mechanism of action in skin wound healing is unclear. The Wnt/β-catenin signaling pathway plays a positive role in the wound healing process. This study aimed to investigate the effects of esculin on the rate and quality of skin wound healing in mice and explore its regulatory role in the Wnt/b-catenin signaling pathway. MATERIAL AND METHODS: Circular full-thickness skin wounds with a diameter of 8 mm were created on the backs of C57BL/6 mice, which were administered with 20 and 40 mg•kg(-1) esculin through gastric lavage. Wound healing was monitored, and samples collected on day 14 were analyzed through hematoxylin-eosin and Masson staining to assess granulation tissue formation and collagen deposition. Immunohistochemistry, immunofluorescence, and Western blot evaluated markers of collagen synthesis, proliferation, angiogenesis, and proteins in the Wnt/b-catenin signaling pathway. National institutes of health/3T3 cells treated with esculin (50 and 200 μM) were analyzed for proliferating cell nuclear antigen (PCNA) expression to assess proliferative activity. RESULTS: Compared with the model group, the esculin-treated groups exhibited significantly enhanced wound healing (P < 0.05), increased skin epithelial thickness (P < 0.01), and promoted extracellular matrix formation in mice. In addition, esculin significantly raised type I collagen alpha-1 chain and type III collagen alpha-1 chain protein levels (P < 0.05), boosted the expression of the cell proliferation marker PCNA and the vascular marker cluster of differentiation 31 in the dermis (P < 0.05), and upregulated proteins related to the Wnt/b-catenin signaling pathway and increased glycogen synthase kinase 3 beta phosphorylation in skin wound and NIH/3T3 cells (P < 0.05). CONCLUSION: Esculin could upregulate and activate the Wnt/b-catenin signaling pathway to promote wound healing.