(P26-036-25) Therapeutic Potential of Umbelliferone in Maintaining Epidermal Barrier Integrity by Regulating Mitochondrial Homeostasis and Inhibiting Apoptosis in Diabetic Skins

Objectives: Type 2 diabetes elevates oxidative stress and reactive oxygen species (ROS) production, primarily due to sustained hyperglycemia. Mitochondrial dysfunction, a key consequence of diabetes, disrupts cellular metabolism and exacerbates ROS overproduction, leading to apoptotic cell death and impaired epidermal barrier function in keratinocytes. This study evaluated the effects of umbelliferone on high-glucose (HG)-induced ROS formation, mitochondrial dysfunction, and epidermal barrier disruption.

Methods: HaCaT cells were cultured in HG media with varying umbelliferone concentrations for three days. A type 2 diabetic mouse model was established using a high-fat diet and streptozotocin injection, followed by 10-week oral umbelliferone treatment (10 mg/kg). ROS formation was assessed via dihydroethidium (DHE) staining. Expression levels of mitochondrial biogenesis proteins (PGC-1α, NRF-1, TFAM, PINK1, Mfn-1), apoptosis markers (Bax, Bcl-2, cytochrome c), and cell adhesion junction proteins (ZO-1, Occludin) were analyzed in HaCaT cells and diabetic skin tissues.

Results: High glucose significantly increased ROS production and downregulated mitochondrial biogenesis proteins in HaCaT cells and diabetic skin tissues, effects counteracted by umbelliferone. Umbelliferone also reduced pro-apoptotic markers (Bax, cytochrome c), upregulated the anti-apoptotic protein Bcl-2, and restored ZO-1 and Occludin expression. These findings indicate umbelliferone's potential to mitigate oxidative stress, maintain mitochondrial function, and preserve epidermal barrier integrity.

Conclusions: Umbelliferone effectively counteracts HG-induced oxidative stress, restores mitochondrial function, regulates apoptosis, and improves epidermal barrier function in keratinocytes and diabetic skin tissues

Funding Sources: This work was supported by NRF grants funded by the Korean government (2022R1I1A1A01067661, 2021R1I1A0104231612).