Wound healing activity of Sweetgum oil (Liquidambar orientalis L. balsam): characterization of its mechanism of action on HaCaT human keratinocyte cells and possible responsible active constituents

Background: Sweetgum oil (Liquidambar orientalis Mill.; Styrax liquidus) is traditionally used in Turkey for wounds and burns, yet its cellular mechanisms remain unclear. Methods: Two locally sourced sweetgum oil samples were tested in human HaCaT keratinocytes. Cytotoxicity was assessed by MTT. Proliferation and migration were quantified using RTCA-DP and scratch assays. COL1A1 mRNA was measured by TaqMan RT-PCR. Phytochemical profiling employed IT-TOF/MS; titrated Centella asiatica extract (TECA) was the positive control. Results: Non-toxic concentrations were identified at 0.001–0.1 μg/mL. At 0.001 μg/mL, sweetgum oil significantly increased keratinocyte proliferation and migration in a time-dependent manner (RTCA-DP; p < 0.05 to p < 0.01), accelerating scratch-wound closure versus control. COL1A1 expression was unchanged. IT-TOF/MS indicated phenylpropyl cinnamate as the dominant constituent in both samples. Conclusions: Sweetgum oil promotes re-epithelialization-related processes primarily by enhancing keratinocyte proliferation and migration rather than collagen induction. These findings support sweetgum oil as a promising natural wound-healing agent and motivate in vivo validation.