黑色素的生成代谢机制及研究方法进展

doi:10.3969/j.issn.2097-2806.2023.10.011

摘要/Abstract

摘要：

随着时代的发展，“以白为美”思潮在近几年迎来了高涨期，美白市场空前繁荣。黑色素合成代谢过程在很大程度上调控着皮肤的颜色，因此美白剂的开发主要依赖于活性物质对黑色素的调节作用。本文将黑色素的合成、转运以及代谢过程细分为以下五个步骤：1）黑素细胞内黑素小体的装配；2）黑素小体的成熟及黑素的合成；3）成熟的黑素小体向黑素细胞树突状远端移动；4）黑素小体转移至角质形成细胞；5）黑素小体在角质形成细胞中的再分布或降解、排出。结合以上五个步骤的最新研究进展对其关键机制、重要标志物以及检测方法进行总结阐述，为美白剂的开发提供更加具体且科学的理论基础及开发思路。

关键词: 美白, 黑素细胞, 黑素体, 黑色素生成

Abstract:

With the development of the times, the market demand of whitening agent is increasing day by day, which has a high development value. Skin color mainly depends on the proportion of true melanin and brown melanin, as well as the number, size, distribution and degree of melanization of melanosomes, so the development of whitening active substances mainly depends on the process of melanin production. Based on this, this paper focuses on the literature reports in the past few years, summarizes and discusses the latest progress in the regulation process of melanin production in five steps, and summarizes the key regulation signal pathways, important markers and their detection methods from the regulation mechanism. It provides a theoretical basis for the development of whitening products from a more comprehensive and specific perspective. Finally, with reference to the action mechanism of different stages of melanogenesis, the different ways and current research progress of the development of whitening active components are summarized. The combined use of whitening active ingredients can play a greater whitening effect to a certain extent, and it has gradually become the development trend of whitening agents. This paper can provide a reference for melanin production through the regulation of different stages of melanin, and provide a more scientific research and development direction for whitening products.

Key words: whitening, melanocyte, melanosome, melanogenesis

中图分类号:

TQ658

杨小玉, 刘金俊, 刘蕾, 何聪芬, 毕永贤, 李昊. 黑色素的生成代谢机制及研究方法进展[J]. 日用化学工业（中英文）, 2023, 53(10): 1194-1203.

Yang Xiaoyu, Liu Jinjun, Liu Lei, He Congfen, Bi Yongxian, Li Hao. Progress in metabolic mechanism and research methods of melanin production[J]. China Surfactant Detergent & Cosmetics, 2023, 53(10): 1194-1203.

图/表 4

表1

图1

图2

表2

美白开发路径及进展"

步骤	黑色素合成阶段	相关因素	作用机理	活性成分示例
1	黑素细胞内黑素体的装配	ILK	保留未成熟的黑素体至核周区域	未开发
		TYR的合成装配	细胞内pH值变化的影响TYR向黑素体的运输	聚甲氧基黄酮混合物^[40]
		Pmel17（gp100）	形成Ⅱ期黑素体的内部纤维状基质	未开发
2	黑素小体的成熟及黑素的合成	外界刺激（紫外、压力等）	抑制光传导信号通路（如ORAI1），降低黑色素合成水平	茴香提取物^[11]、番石榴叶^[41]
		旁分泌因子	角质形成细胞和成纤维细胞等分泌的调控因子、自由基、炎症因子等刺激黑素细胞黑素生成反应	绿茶^[42]、灵芝多糖^[43]
		胞内信号传导	细胞内黑素生成信号通路刺激黑素生成	甘草^[44]、乙酰水杨酸^[45]
		黑素合成相关酶	通过抑制细胞内黑素合成相关酶活性及其基因表达水平调节黑色素合成	熊果苷^[46]、曲酸^[47]、光甘草定^[48]、苯乙基间苯二酚^[49]、鞣花酸^[50]、红参提取物^[51]、睡莲提取物^[52]
		黑素还原剂	将已形成的黑色素还原呈无色	维生素E^[53]
3	成熟黑素小体向黑素细胞树突状远端移动	微管运输网络	驱动蛋白和动力蛋白控制微管中黑素体的双向运动和定位	未开发
3	成熟黑素小体向黑素细胞树突状远端移动	肌动蛋白纤维运输网络	Rab27A复合物调控肌动蛋白纤维转运，调节黑素体运输	大蕉（MUSASAPIENTUM）果提取物^[54]
4	黑素小体转移至角质形成细胞	蛋白酶激活受体2（PAR-2）	角质形成细胞内产生的七跨膜G蛋白偶联受体，介导黑素体转移	烟酰胺及其衍生物^[55]、大豆/牛奶提取物^[56]
		α-促黑素细胞激素（α-MSH）	刺激成熟黑素体从黑素细胞转移至周围的角质形成细胞中	红南瓜籽提取物^[23]
		树突数量及长短	Rho和Rac家族是树突形成的主要调节因子	人参皂苷F1^[26]
5	黑素小体在角质形成细胞中的再分布或降解、排除	溶酶体水解酶	溶酶体水解酶在黑素随角质形成细胞上移过程中对黑素体进行降解	异甘草素^[57]
		自噬相关蛋白（如ATG7、LC3...）	自噬通过调节角质形成细胞中的黑素体降解	茶碱^[34]、异甘草素^[36]
		表皮重塑和脱屑	加速皮肤更新速度	乙醇酸、乳酸^[58]

表2

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批准年份/年	INCI名称/物质名称	原料名称	主要作用机制
1983	Magnesium Ascorbyl Phosphate	抗坏血酸磷酸脂镁	抑制酪氨酸酶活性
1988	Kojic Acid	曲酸	抑制酪氨酸酶活性
1989	Arbutin	熊果苷	抑制酪氨酸酶活性
1994	Ascorbyl Glucoside	抗坏血酸葡萄糖苷	抑制酪氨酸酶活性
1997	Ellagic Acid	鞣花酸	抑制酪氨酸酶活性
1998	Rucinol^?	芸香醇^?	抑制酪氨酸酶活性
1999	Chrysanthellum Indicum	洋甘菊	内皮素阻滞剂
2001	Linoleic Acid	亚油酸	降解酪氨酸酶，刺激表皮更新
2002	Tranexamic Acid	氨甲环酸	抑制前列腺素E2（PGE2）的产生
2003	Potassium Methoxysalicylate	甲氧基水杨酸钾	抑制酪氨酸酶活性
2004	Vitamin C Ethyl	3-O-乙早抗坏血酸醚	抑制酪氨酸酶活性
2004	Adenosine Mono Phosphate	Energy signal AMP^?	加速表皮更新
2005	5,5-dipropyl-biphenyl-2,2-diol	Magnolignan^?	抑制酪氨酸酶活性
2007	Niacinamide	烟酰胺	抑制黑素体转移
2008	4-（4-hydroxyphenyl）-2-butanol	Rhododenol^?	抑制酪氨酸酶活性
2008	Tranexamic Acid Cetyl Ester Hydrochloride	TXC	抑制前列腺素E2（PGE2）的产生
2009	Ascorbyl Tetraisopalmitate	抗坏血酸四异棕榈酸酯	抑制酪氨酸酶活性
2018	Dexpanthenol	Dexpanthenol W （PCE-DP）	加速表皮新陈代谢