Gunia-Krzyżak Agnieszka, Popiol Justyna, Marona Henryk
Laboratory of Cosmetic Chemistry, Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland..
Curr Med Chem. 2016;23(31):3548-3574. doi: 10.2174/0929867323666160627094938.
Hyperpigmentation disorders constitute important medical and aesthetical conditions. Dark areas or dark spots on the skin result from inappropriate amount and/or deposition of skin pigments - melanins. Several depigmenting agents, such as kojic acid, arbutin, aloesin, ellagic acid, resveratrol, azelaic acid, niacinamide, tretinoin, glycolic acid, lactic acid, and citric acid, have already been identified and are used in topical drugs or cosmetic formulations for the treatment of hyperpigmentations. However, these compounds are characterized by insufficient effectiveness and multiple adverse effects. As a result, there is still a need for searching for new active substances. The current paper summarizes strategies for searching for novel melanogenesis inhibitors. In the review, they are divided according to approach, into in silico, in vitro and in vivo experiments. In silico research includes computational studies with models of tyrosinase and di-copper complexes. The in vitro approach is based on tests using tyrosinase (a key enzyme in melanin biosynthesis), cell cultures, cell co-cultures, pigmented human skin equivalents or Streptomyces bikiniensis model. In vivo studies involve zebrafish, rodents or humans. Examples of protocols and laboratory procedures are presented, with a focus on utilization of various models for evaluation of mechanisms of action of tested compounds. The potential limitations of the methods are also discussed, together with future perspectives in the field of searching for melanogenesis inhibitors.
色素沉着紊乱是重要的医学和美学问题。皮肤出现深色区域或黑斑是由于皮肤色素——黑色素的量不当和/或沉积所致。几种脱色剂，如曲酸、熊果苷、芦荟素、鞣花酸、白藜芦醇、壬二酸、烟酰胺、维甲酸、乙醇酸、乳酸和柠檬酸，已被确定并用于局部用药或化妆品配方中治疗色素沉着。然而，这些化合物的特点是疗效不足且有多种不良反应。因此，仍需要寻找新的活性物质。本文总结了寻找新型黑色素生成抑制剂的策略。在这篇综述中，它们根据方法分为计算机模拟、体外和体内实验。计算机模拟研究包括使用酪氨酸酶和双铜配合物模型的计算研究。体外方法基于使用酪氨酸酶（黑色素生物合成中的关键酶）、细胞培养、细胞共培养、色素沉着的人体皮肤等效物或比基尼链霉菌模型的测试。体内研究涉及斑马鱼、啮齿动物或人类。文中给出了实验方案和实验室操作的示例，重点是利用各种模型评估受试化合物的作用机制。还讨论了这些方法的潜在局限性以及寻找黑色素生成抑制剂领域的未来前景。
