期刊
AGING-US
卷 13, 期 23, 页码 25325-25341出版社
IMPACT JOURNALS LLC
关键词
artesunate; skin photoaging; beta-catenin; ultraviolet radiation; cell senescence
资金
- National Natural Science Foundation of China [81674039, 81873347]
- Key Projects of Scientific Research Fund of Traditional Chinese Medicine of Hubei Health Commission [ZY2021Z011]
- Training Project Funding Plan of Young-aged Talent of Health System in Hubei Province (2020-2023)
- Research and Innovation Fund for Graduate Students of Jianghan University [211051001]
- key project of Chongqing Science and Health Joint Medicine in 2022 [2022ZDXM037]
The semi-synthetic derivative of artemisinin, artesunate, has been shown to alleviate UVB irradiation-induced skin photoaging by suppressing cell senescence, intracellular ROS production, p16(INK4a) expression, and apoptosis, and promoting proliferation and expression of SOD and beta-catenin in HaCaT cells. These results offer novel insights into the pharmacological activity of artesunate.
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.
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