Wound Healing Activity and Molecular Mechanisms of Aralia cordata Ethanol Extract

Aralia cordata has been traditionally used as an edible and medicinal plant and is known to possess antioxidant and anti-inflammatory properties. However, its wound healing activity and underlying molecular mechanisms have not been fully elucidated. This study evaluated the antioxidant activity and wound-healing potential of Aralia cordata ethanol extract (AC-EE) in HaCaT keratinocytes. Antioxidant activity was assessed using ABTS and DPPH radical scavenging assays, while cell viability and proliferation were examined by MTT assay. Wound-healing activity was evaluated by scratch assay, and the expression of wound-healing-related genes was analyzed by RT-qPCR. In addition, AP-1 luciferase reporter assay and Western blot analysis were performed to investigate changes in AKT/ERK signaling activity and AP-1 transcriptional activity. The AKT and ERK signaling pathways are known to regulate keratinocyte proliferation, migration, and survival, and changes in these signaling pathways have been associated with AP-1-mediated regulation of genes involved in cellular responses. AC-EE exhibited concentration-dependent antioxidant activity and showed no significant cytotoxicity within the tested concentration range. It significantly promoted keratinocyte proliferation and accelerated wound closure, particularly at higher concentrations. Moreover, AC-EE increased the expression of KGF, EGF, Keratin 8 and Keratin 17, enhanced AP-1 transcriptional activity, and upregulated the phosphorylation of AKT and ERK. These findings suggest that AC-EE enhances keratinocyte proliferation and migration, accompanied by alterations in AKT/ERK signaling activity and AP-1 transcriptional activity, indicating its potential as a natural bioactive ingredient for cosmetic applications related to skin repair.