Research Paper Volume 13, Issue 23 pp 25325—25341
Artesunate treatment ameliorates ultraviolet irradiation-driven skin photoaging via increasing β-catenin expression
- 1 Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Huazhong University of Science and Technology, Wuhan 430022, Hubei, China
- 2 Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400000, China
- 3 College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
- 4 Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
Received: September 15, 2021 Accepted: November 24, 2021 Published: December 9, 2021
https://doi.org/10.18632/aging.203749How to Cite
Copyright: © 2021 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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/cm2) for 5 days. HaCaT cells were pretreated with three concentrations of Art (1, 5 and 20 μg/ml) for 2 h each day. After 5 days, cell senescence, ROS production, SOD levels, p16INK4a and β-catenin expression, proliferation and apoptosis were detected in HaCaT cells. Effects of Art on normal cells were investigated. After sh-β-catenin transfection or XAV-939 treatment, HaCaT cells were pretreated with 20 μg/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 β-catenin silencing on skin photoaging were investigated.
Results: Art treatment suppressed cell senescence, intracellular ROS production, p16INK4a expression and apoptosis and promoted proliferation and SOD and β-catenin expression in UVB irradiated HaCaT cells. But Art had no toxic effects on normal cells. Silencing β-catenin by sh-β-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 β-catenin expression, which offered novel clues for pharmacological activity of Art.
Abbreviations
UVB: ultraviolet B; ROS: reactive oxygen species; SOD: superoxide dismutase; Art: Artesunate; MTT: Methyl Thiazolyl Tetrazolium; TC50: median toxic concentration; SA-β-gal: Senescence-associated β-galactosidase; CCK-8: Cell counting kit-8; TUNEL: TdT-mediated dUTP Nick-End Labeling; sh-β-catenin: shRNA against β-catenin; sh-NC: shRNA negative control.