Abstract
The chronic exposure of skin to ultraviolet (UV) radiation causes adverse dermal reactions, such as erythema, sunburn, photoaging, and cancer, by altering several signalling pathways associated with oxidative stress, inflammation, and DNA damage. One of the possible UV light protection strategies is the use of dermal photoprotective preparations. The plant hormone kinetin (N6-furfuryladenine; KIN) exhibits antioxidant and anti-senescent effects in human cells. Topically applied KIN also reduced some of the clinical signs of photodamaged skin. To improve the biological activities of KIN, several derivatives have been recently prepared and their beneficial effects on cell viability of skin cells exposed to UVA and UVB light were screened. Two potent candidates, 6-(tetrahydrofuran-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO) and 6-(thiophen-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO6), were identified. Here the effects of KIN, its N9-substituted derivatives the tetrahydropyran-2-yl derivative of KIN (THP), tetrahydrofuran-2-yl KIN (THF), HEO and HEO6 (both THF derivatives) on oxidative stress, apoptosis and inflammation in UVA- or UVB-exposed skin cell was investigated. Human primary dermal fibroblasts and human keratinocytes HaCaT pre-treated with the tested compounds were then exposed to UVA/UVB light using a solar simulator. All compounds effectively prevented UVA-induced ROS generation and glutathione depletion in both cells. HEO6 was found to be the most potent. All compounds also reduced UVB-induced caspase-3 activity and interleukin-6 release. THP and THF exhibited the best UVB protection. In conclusion, our results demonstrated the UVA- and UVB-photoprotective potential of KIN and its derivatives. From this point of view, they seem to be useful agents for full UV spectrum protective dermatological preparations.
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23 January 2023
A Correction to this paper has been published: https://doi.org/10.1007/s43630-023-00380-x
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Acknowledgements
We would like to express our thanks to Iveta Hatalová (University Hospital Olomouc) for support with the recruitment of skin tissue donors. This study was financially supported by the Grant IGA_LF_2022_025 and IGA_PrF_2022_012 and the Institutional Support of Palacký University, Olomouc - RVO 61989592.
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ARS and JV designed the experiments, performed some experiments (ROS generation, GSH and caspase-3 level) and wrote the main manuscript. DŠ was responsible for preparation of cell cultures, viability and ELISA assays. MH was responsible for test compounds synthesis and purification and for preparation of the manuscript. BZ was responsible for recruitment of skin tissue donors and sample collection. LP was responsible for critical proofreading of data and the text of the manuscript. All authors contributed to data analysis and manuscript writing. All authors read and approved the final manuscript.
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The authors have no relevant financial or non-financial interests to disclose. The photoprotective properties of new derivatives were the subject of the below patent applications: Hönig, M.; Plíhalová, L.; Doležal, K.; Voller, J.; Strnad, M.; Spíchal L.; Vostálová, J.; Rajnochová Svobodová, A.; Ulrichová J.; Kadlecová A.; Plíhal O. Adenine derivatives and their use as UV-photoprotective agents. PCT application WO2017036434A1, 2017. Hönig, M.; Plíhalová, L.; Doležal, K.; Voller, J.; Strnad, M.; Spíchal L.; Vostálová, J.; Rajnochová Svobodová, A.; Ulrichová J.; Kadlecová A.; Plíhal O. Adenine derivatives and their use. Czech Republic. Patent no. 307722, 2019. Hönig, M.; Plíhalová, L.; Doležal, K.; Voller, J.; Strnad, M.; Spíchal L.; Vostálová, J.; Rajnochová Svobodová, A.; Ulrichová J.; Kadlecová A.; Plíhal O. Adenine derivatives and their use as UV-photoprotective agents. United States. Patent no. US10774084, 2020.
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The Ethics Committee of University Hospital Olomouc and the Faculty of Medicine and Dentistry, Palacký University, Olomouc approved the use of superfluous skin from human volunteers (ref. number 41/09). All volunteers gave their written informed consent.
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Vostálová, J., Škařupová, D., Plíhalová, L. et al. Photoprotective properties of new derivatives of kinetin. Photochem Photobiol Sci 22, 357–369 (2023). https://doi.org/10.1007/s43630-022-00320-1
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DOI: https://doi.org/10.1007/s43630-022-00320-1