Abstract

Melanin is the main pigment of human skin, playing the primary role of protection from ultraviolet radiation. Alteration of the melanin production may lead to hyperpigmentation diseases, with both aesthetic and health consequences. Thus, suppressors of melanogenesis are considered useful tools for medical and cosmetic treatments. A great interest is focused on natural sources, aimed at finding safe and quantitatively available depigmenting substances. Lichens are thought to be possible sources of this kind of compounds, as the occurrence of many phenolic molecules suggests possible effects on phenolase enzymes involved in melanin synthesis, like tyrosinase. In this work, we used four lichen species, Cetraria islandica Ach., Flavoparmelia caperata Hale, Letharia vulpina (L.) Hue, and Parmotrema perlatum (Hudson) M. Choisy, to obtain extracts in solvents of increasing polarity, viz. chloroform, chloroform-methanol, methanol, and water. Cell-free, tyrosinase inhibition experiments showed highest inhibition for L. vulpina methanol extract, followed by C. islandica chloroform-methanol one. Comparable results for depigmenting activities were observed by means of in vitro and in vivo systems, such as MeWo melanoma cells and zebrafish larvae. Our study provides first evidence of depigmenting effects of lichen extracts, from tyrosinase inhibition to cell and in vivo models, suggesting that L. vulpina and C. islandica extracts deserve to be further studied for developing skin-whitening products.

Highlights

  • In vertebrates, melanin synthesis is realized by specialized cells called melanocytes, within lysosome-like organelles called melanosomes

  • Melanization is controlled by different processes, including environmental (e.g., UV rays) and endogenous (e.g., α-MSH) factors, stimulation of melanocortin-1 receptor (MC1R), signal transduction by cAMP and MAPK pathways, activation of microphthalmia-associated transcription factor (MITF), and expression of premelanosome protein (Pmel), tyrosinase (TYR), and tyrosinase-related proteins (TYRP1) (D’Mello et al, 2016; Cheli et al, 2010)

  • Thalli of F. caperata and of P. perlatum were collected in a woodland area of eastern Liguria (NW Italy), L. vulpina in a forest area of Valtournenche (NE Valle d’Aosta, Italy), and C. islandica was purchased from Kubja Ürditalu (Tallinn, Estonia)

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Summary

Introduction

Melanin synthesis is realized by specialized cells called melanocytes, within lysosome-like organelles called melanosomes. Tyrosinase (EC1.14.18.1) is a key enzyme of melanin synthesis and has been widely investigated as a target of modulatory agents of melanization. It is a multifunctional copper-containing enzyme, widely distributed in nature, responsible for melanization in animals and for browning in plants and microorganism (Kondo & Hearing, 2011). The enzyme catalyzes two distinct reactions of melanin formation: hydroxylation of tyrosine by monophenolase activity, and oxidation of 3,4-dihydroxyphenylalanine (L-DOPA) to o-dopaquinone by diphenolase action. These reactive o-quinones undergo non-enzymatical polymerization to form melanin

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