Lactobacillus helveticus-Fermented Milk Whey Suppresses Melanin Production by Inhibiting Tyrosinase through Decreasing MITF Expression.

Nobutomo Ikarashi,Misaki Hatanaka,Risako Kon,Natsuko Fukuda,Mami Sasaki,Hiroyasu Sakai,Makiba Ochiai,Junzo Kamei

doi:10.3390/nu12072082

Abstract

Whey obtained from milk fermented by the Lactobacillus helveticus CM4 strain (LHMW) has been shown to improve skin barrier function and increase skin-moisturizing factors. In this study, we investigated the effects of LHMW on melanin production to explore the additional impacts of LHMW on the skin. We treated mouse B16 melanoma cells with α-melanocyte-stimulating hormone (α-MSH) alone or simultaneously with LHMW and measured the amount of melanin. The amount of melanin in B16 cells treated with α-MSH significantly increased by 2-fold compared with that in control cells, and tyrosinase activity was also elevated. Moreover, treatment with LHMW significantly suppressed the increase in melanin content and elevation of tyrosinase activity due to α-MSH. LHMW also suppressed the α-MSH-induced increased expression of tyrosinase, tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) at the protein and mRNA levels. Furthermore, the mRNA and protein microphthalmia-associated transcription factor (MITF) expression levels were significantly increased with treatment with α-MSH alone, which were also suppressed by LHMW addition. LHMW suppression of melanin production is suggested to involve inhibition of the expression of the tyrosinase gene family by lowering the MITF expression level. LHMW may have promise as a material for cosmetics with expected clinical application in humans.

Highlights

Effect of LHMW on Melanin Production Stimulated by α-melanocyte-stimulating hormone (α-MSH)
We investigated the effect of LHMW on melanin production stimulated by α-MSH
Expression to suppress melanin production. These results indicated that suppressed tyrosinase protein expression was associated with the inhibitory effect of LHMW on tyrosinase activity

Summary

Introduction

Melanin, which is the end product of melanogenesis, is generated in the melanosomes of melanocytes and is an important factor determining the color of human skin, hair, and eyes [1,2].Melanin is associated with protection of the skin from ultraviolet rays; excess melanin production and accumulation on the skin cause pigmentation disorders, such as freckles, skin discoloration, and pigmented age spots [3].In addition to ultraviolet irradiation, melanin production is induced by various hormones, including α-melanocyte-stimulating hormone (α-MSH) and estrogen [4,5], as well as by environmental stimulation from chemical substances such as theophylline [6,7] and extracellular stimuli, such as cytokines [8]. Melanin, which is the end product of melanogenesis, is generated in the melanosomes of melanocytes and is an important factor determining the color of human skin, hair, and eyes [1,2]. Tyrosinase is a rate-limiting enzyme of the melanin production pathway, in which l-tyrosine is converted to l-3,4-dihydroxyphenylalanine (l-DOPA) via hydroxylation. DCT, which is called TRP2, catalyzes the tautomerization of dopachrome to produce 5,6-dihydroxyindole-2-carboxylic acid (DHICA) [11]. TRP1 oxidizes DHICA to produce carboxylate indole-quinone [12]. TRP1 and DCT function downstream from tyrosinase in the melanin biosynthesis pathway [2]. These enzymes are suitable targets for the development of cosmetics aimed at skin whitening, and such novel materials have been actively explored [13,14]

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Conclusion