Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti‑melanogenic effects were investigated against the background of skin photoprotective and anti‑melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA‑and UVB‑irradiated keratinocytes and α‑melanocyte stimulating hormone (α‑MSH)‑stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti‑apoptotic effects on UVA‑and UVB‑irradiated keratinocytes. After α‑MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α‑MSH‑induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia‑associated transcription factor (MITF), tyrosinase, tyrosinase‑related protein (TRP)‑1 and TRP‑2 in α‑MSH‑stimulated melanocytes. In addition, gomisin D markedly downregulated α‑MSH‑induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP‑1 and TRP‑2 genes. Overall, gomisin D has photoprotective and anti‑melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.

中文翻译：

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gomisin D、J 和 O 的光保护和抗黑色素生成特性的比较研究。

皮肤癌是全世界最常见的人类恶性肿瘤，已知太阳紫外线 (UV) 辐射在其发病机制中起重要作用。在皮肤光保护和抗黑色素生成特性的背景下，研究了具有抗氧化、光保护和抗黑色素生成作用的天然候选化合物。Gomisin D、J 和 O 是Kadsura中存在的二苯并环辛二烯木脂素药用植物，具有多种药理活性。在这项研究中，探索了 gomisin D、J 和 O 在 UVA 和 UVB 照射的角质形成细胞和 α-黑色素细胞刺激素 (α-MSH) 刺激的黑色素细胞中的作用和机制。在 UVA 和 UVB 照射后，用 gomisin D、J 和 O 处理角质形成细胞，并检查角质形成细胞的活力、乳酸脱氢酶 (LDH) 的释放、细胞内活性氧 (ROS) 的产生和细胞凋亡。结果表明，在 UVA 和 UVB 照射下，gomisin D 和 J 提高了角质形成细胞的活力并减少了 LDH 的释放。gomisin D 和 J 抑制了由 UVA 和 UVB 照射诱导的细胞内 ROS 产生。此外，Annexin V 和 TUNEL 染色分析表明，gomisin D 和 J 对 UVA 和 UVB 照射的角质形成细胞具有显着的抗凋亡作用。在 α-MSH 刺激后，用 gomisin D、J 和 O 处理黑素细胞，并检查黑素细胞活力、细胞内黑色素含量、细胞内酪氨酸酶活性的变化以及这些变化背后的机制。Gomisin D 显着抑制 α-MSH 诱导的细胞内黑色素含量和酪氨酸酶活性增加。从机制上讲，gomisin D 降低了 α-MSH 刺激的黑素细胞中小眼相关转录因子 (MITF)、酪氨酸酶、酪氨酸酶相关蛋白 (TRP)-1 和 TRP-2 的蛋白质和 mRNA 表达水平。此外，gomisin D 显着下调 α-MSH 诱导的蛋白激酶 A 和 cAMP 反应元件结合蛋白的磷酸化，已知它们存在于 MITF、酪氨酸酶、TRP-1 和 TRP-2 基因的上游。总体而言，gomisin D 具有光保护和抗黑色素生成作用；这些发现为使用天然化合物（如 gomisin D）生产潜在的增白剂和光保护剂提供了基础。