Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

Kuo-Ching Wen,Wan-Chen Wu,Yin-Chih Chien,Hsiao-Wen Wang,Chin-Sheng Wu,Chih-Shiang Chang,Hsiu-Mei Chiang

doi:10.3390/ijms141223420

Kuo-Ching Wen, Wan-Chen Wu + Show 5 more

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https://doi.org/10.3390/ijms141223420

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Abstract

Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

Highlights

Melanin is essential for protecting skin against UV irradiation damage, abnormal melanin production can lead to hyperpigmentation disorders such as freckles, melanoma, and other types of skin cancer [1,2,3]
Ultraviolet (UV) irradiation stimulates the secretion of α-melanocyte-stimulating hormone (α-MSH), which binds to the melanocortin 1 receptor (MC1R)
We found that tyrosol and its analogues inhibited melanin content in B16F0 cells by inhibiting tyrosinase and tyrosinase-related protein 1 (TRP-1) expression but not tyrosinase-related protein 2 (TRP-2) or microphthalmia-associated transcription factor (MITF)

Summary

Introduction

Melanin is essential for protecting skin against UV irradiation damage, abnormal melanin production can lead to hyperpigmentation disorders such as freckles, melanoma, and other types of skin cancer [1,2,3]. Tyrosinase is a key enzyme in the biosynthesis of melanin and is involved in determining the color of mammalian skin and hair [4,5]. Ultraviolet (UV) irradiation stimulates the secretion of α-melanocyte-stimulating hormone (α-MSH), which binds to the melanocortin 1 receptor (MC1R). It results in the activation of microphthalmia-associated transcription factor (MITF), which induces the expression of tyrosinase, TRP-1, and TRP-2 [7]. The mechanisms of action of many skin-lightening agents are believed to involve in the down-regulation of melanin synthesis, the inhibition of tyrosinase activity, and inhibition of melanosome transfer [1,5]

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