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Hypopigmenting agents: an updated review on biological, chemical and clinical aspects

机译：色素沉着剂：有关生物学，化学和临床方面的最新评论

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摘要

An overview of agents causing hypopigmentation in human skin is presented. The review is organized to put forward groups of biological and chemical agents. Their mechanisms of action cover (i) tyrosinase inhibition, maturation and enhancement of its degradation; (ii) Mitf inhibition; (iii) downregulation of MC1R activity; (iv) interference with melanosome maturation and transfer; (v) melanocyte loss, desquamation and chemical peeling. Tyrosinase inhibition is the most common approach to achieve skin hypopigmentation as this enzyme catalyses the rate-limiting step of pigmentation. Despite the large number of tyrosinase inhibitors in vitro, only a few are able to induce effects in clinical trials. The gap between in-vitro and in-vivo studies suggests that innovative strategies are needed for validating their efficacy and safety. Successful treatments need the combination of two or more agents acting on different mechanisms to achieve a synergistic effect. In addition to tyrosinase inhibition, other parameters related to cytotoxicity, solubility, cutaneous absorption, penetration and stability of the agents should be considered. The screening test system is also very important as keratinocytes play an active role in modulating melanogenesis within melanocytes. Mammalian skin or at least keratinocytes/melanocytes co-cultures should be preferred rather than pure melanocyte cultures or soluble tyrosinase.
机译：概述了导致人类皮肤色素沉着不足的物质。审查的目的是提出生物和化学制剂的团体。它们的作用机理包括：（i）酪氨酸酶的抑制，成熟和降解的增强; （ii）抑制Mitf; （iii）下调MC1R活性; （iv）干扰黑素体的成熟和转移; （v）黑色素细胞损失，脱皮和化学脱皮。酪氨酸酶抑制是实现皮肤色素沉着最常见的方法，因为该酶催化色素沉着的限速步骤。尽管体外有大量的酪氨酸酶抑制剂，但只有少数能够在临床试验中诱导作用。体外研究与体内研究之间的差距表明，需要新颖的策略来验证其有效性和安全性。成功的治疗方法需要将两种或多种作用于不同机制的药物结合使用，以达到协同作用。除酪氨酸酶抑制作用外，还应考虑与细胞毒性，溶解度，皮肤吸收，渗透和稳定性有关的其他参数。筛选测试系统也非常重要，因为角质形成细胞在调节黑色素细胞内的黑色素生成中起积极作用。应当优选哺乳动物皮肤或至少角质形成细胞/黑素细胞共培养，而不是纯黑素细胞培养或可溶性酪氨酸酶。

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