Madecassoside attenuated UVB irradiation-induced skin ferroptosis by targeting POR.

BACKGROUND

UVB exposure induces oxidative damage and accelerates skin photoaging. Madecassoside (MA), a triterpenoid saponin from Centella asiatica (L.) Urban, has antioxidant and anti-inflammatory properties, but its role in ferroptosis remains unclear.

PURPOSE: This study aims to investigate the effects of MA against UVB-induced ferroptosis and elucidate its underlying mechanisms.

STUDY

DESIGN

Skin cells and a UVB-irradiated mouse model were established to assess the effects of MA on UVB-induced ferroptosis and skin damage.

METHODS

Skin cells and a UVB-irradiated mouse model were used to assess MA's effects on ferroptosis. ROS, lipid ROS, mitochondrial membrane potential and antioxidant enzyme activity were measured. Protein and gene expression of ferroptosis markers were analyzed via Western blot and qPCR. Transmission electron microscopy (TEM) examined mitochondrial morphology.

RESULTS

UVB irradiation induced ferroptosis in human skin cells, characterized by lipid peroxidation, ROS accumulation, mitochondrial dysfunction, and antioxidant depletion. MA treatment significantly inhibited ferroptosis and restored redox balance. In mice, topical MA application enhanced collagen deposition, reduced epidermal thickening, and alleviated ferroptosis. Mechanistically, MA bound to and downregulated the NADPH-cytochrome P450 reductase (POR), a key regulator of ferroptosis and POR overexpression negated MA's protective effects.

CONCLUSION

This study demonstrates that MA protects against UVB-induced ferroptosis via POR inhibition, highlighting its potential for therapeutic and cosmetic applications in preventing ferroptosis.