Vostálová Jitka, Škařupová Denisa, Plíhalová Lucie, Hönig Martin, Zálešák Bohumil, Rajnochová Svobodová Alena
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University Olomouc, Hněvotínská 3, 775 15, Olomouc, Czech Republic.
Department of Chemical Biology, Faculty of Science, Palacký University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic.
Photochem Photobiol Sci. 2023 Feb;22(2):357-369. doi: 10.1007/s43630-022-00320-1. Epub 2022 Oct 20.
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.
皮肤长期暴露于紫外线（UV）辐射会通过改变与氧化应激、炎症和DNA损伤相关的多种信号通路，引发不良的皮肤反应，如红斑、晒伤、光老化和癌症。一种可能的紫外线防护策略是使用皮肤光保护制剂。植物激素激动素（N6-呋喃甲基腺嘌呤；KIN）在人类细胞中具有抗氧化和抗衰老作用。局部应用KIN还能减轻光损伤皮肤的一些临床症状。为了提高KIN的生物活性，最近制备了几种衍生物，并筛选了它们对暴露于UVA和UVB光下的皮肤细胞活力的有益影响。确定了两种有效的候选物，6-(四氢呋喃-2-基)甲基氨基-9-(四氢呋喃-2-基)嘌呤（HEO）和6-(噻吩-2-基)甲基氨基-9-(四氢呋喃-2-基)嘌呤（HEO6）。在此研究了KIN及其N9-取代衍生物KIN的四氢吡喃-2-基衍生物（THP）、四氢呋喃-2-基KIN（THF）、HEO和HEO6（均为THF衍生物）对UVA或UVB照射皮肤细胞中氧化应激、细胞凋亡和炎症的影响。然后，用测试化合物预处理的人原代皮肤成纤维细胞和人角质形成细胞HaCaT使用太阳模拟器暴露于UVA/UVB光下。所有化合物均有效预防了两种细胞中UVA诱导的ROS生成和谷胱甘肽消耗。发现HEO6最有效。所有化合物还降低了UVB诱导的半胱天冬酶-3活性和白细胞介素-6释放。THP和THF表现出最佳的UVB防护效果。总之，我们的结果证明了KIN及其衍生物的UVA和UVB光保护潜力。从这个角度来看，它们似乎是用于全光谱紫外线防护皮肤科制剂的有用药物。
