Icaritin alleviates UVB-induced skin damage by inhibiting ferroptosis via modulation of mitochondrial dynamics.

Ultraviolet B (UVB) radiation is the main environmental cause of skin damage, and ferroptosis plays a crucial role in its damage process. This study investigated the protective effects and mechanisms of icaritin (ICT) against UVB-induced skin injury. Our results showed that ICT significantly alleviated UVB-induced cutaneous dryness, erythema, and epidermal hyperplasia in mice, while increasing collagen fiber content. In vitro, ICT restored the viability of UVB-exposed L929 fibroblasts. Meanwhile, ICT significantly inhibited ferroptosis in fibroblasts, manifested by downregulation of COX2, upregulation of GPX4 and FTH1, and reduction of lipid ROS and lipid peroxidation levels. Further investigation revealed that, ICT ameliorated mitochondrial dysfunction by restoring membrane potential, enhancing ATP production, decreasing ROS, and normalizing the NAD+ /NADH ratio. Morphological and protein analysis confirmed that ICT improves mitochondrial homeostasis by regulating mitochondrial dynamics, thereby inhibiting ferroptosis. These findings confirmed that ICT as a promising therapeutic agent for UVB-induced skin damage.