(P06-032-23) Phenolic-Enriched Maple Syrup Extract Alleviates Erastin-Induced Ferroptosis in Human Skin Keratinocytes

Objectives: Ferroptosis, an iron-dependent and lipid peroxidation-regulated type of cell death, is highly involved in a variety of pathological conditions. Published studies revealed that ferroptosis in keratinocytes contributes to the development of skin damage including psoriatic and ultraviolet B radiation-induced inflammation. Our group previously reported that a phenolics-enriched maple syrup extract (MSX), showed protective effects in human skin cells against oxidative stress-induced cell death and anti-inflammatory in murine macrophages. However, it is not clear whether MSX can exert protective effects against ferroptosis in skin cells. Herein, we evaluated MSX’s anti-ferroptotic effect in human keratinocyte HaCaT cells to support that MSX is a promising anti-ferroptotic natural product, which may have nutraceutical and/or cosmeceutical potential for skin health.

Methods: Human keratinocyte HaCaT cells were exposed to erastin with/without MSX for 24 h, anti-ferroptotic effects of MSX were characterized by measuring the level of iron and cellular lipid oxidation in HaCaT cells by flow cytometric and staining assay, respectively. In addition, the modulatory effects of MSX on specific ferroptosis molecular targets analysis was performed to elucidate the mechanisms of MSX’s anti-ferroptotic activity.

Results: Cell death was induced in HaCaT cells by exposure to a known ferroptosis inducer, namely, erastin at a concentration of 20 µM, which reduced the cell viability to 34.4%. Erastin-induced ferroptosis in HaCaT cells was counteracted by the treatment with MSX at concentrations at 50 and 10 µg/mL, which increased the cell viability to 67.1 and 50.5 %, respectively. Fisetin, a natural dietary flavonoid used as the positive control, showed an inhibitory effect on ferroptosis by increasing the cell viability to 57.3% at 2.5 µg/mL.

Conclusions: Our present findings support MSX as a promising anti-ferroptosis natural product that may have nutritional and/or cosmeceutical potential to promote skin health.

Funding Sources: None