Artesunate treatment ameliorates ultraviolet irradiation-driven skin photoaging via increasing beta-catenin expression

Objective: Artesunate, a semi-synthetic derivative of artemisinin, exerts various pharmacological activities. Nevertheless, the effects of Art on skin photoaging remain unclear. Herein, we investigated whether Art ameliorated ultraviolet-irradiated skin photoaging in HaCaT cells and mice. Methods: To construct skin photoaging cellular models, HaCaT cells were irradiated by UV (UVB, 20mJ/cm(2)) for 5 days. HaCaT cells were pretreated with three concentrations of Art (1, 5 and 20 mu g/ml) for 2 h each day. After 5 days, cell senescence, ROS production, SOD levels, p16(INK4a) and beta-catenin expression, proliferation and apoptosis were detected in HaCaT cells. Effects of Art on normal cells were investigated. After sh-beta-catenin transfection or XAV-939 treatment, HaCaT cells were pretreated with 20 ug/ml Art and irradiated by UVB. After 5 days, skin photoaging was then observed. Furthermore, skin photoaging mouse models were established and the effects of Art and beta-catenin silencing on skin photoaging were investigated. Results: Art treatment suppressed cell senescence, intracellular ROS production, p16(INK4a) expression and apoptosis and promoted proliferation and SOD and beta-catenin expression in UVB irradiated HaCaT cells. But Art had no toxic effects on normal cells. Silencing beta-catenin by sh-beta-catenin or XAV-939 exacerbated UVB irradiation-mediated cell senescence, apoptosis, and ROS production in HaCaT cells, which was ameliorated by Art treatment. The therapeutic effects of Art on skin photoaging were also confirmed in mouse models. Conclusions: These findings suggested that Art treatment alleviated UVB irradiation-driven skin photoaging through enhancing beta-catenin expression, which offered novel clues for pharmacological activity of Art.