Anti-Melanogenic Properties of Greek Plants. A Novel Depigmenting Agent from Morus alba Wood.

Eliza Chaita,Emmanuel Mikros,Christina Cheimonidi,George Lambrinidis,Nektarios Aligiannis,Dimitris Beis,Alexios-Leandros Skaltsounis,Ioannis Trougakos,Adamantia Agalou

doi:10.3390/molecules22040514

Eliza Chaita, Emmanuel Mikros + Show 7 more

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https://doi.org/10.3390/molecules22040514

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Abstract

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells. Bioassay-guided isolation led to the acquisition of twelve compounds: oxyresveratrol (1), kuwanon C (2), mulberroside A (3), resorcinol (4), dihydrooxyresveratol (5), trans-dihydromorin (6), 2,4,3′-trihydroxydihydrostilbene (7), kuwanon H (8), 2,4-dihydroxybenzaldehyde (9), morusin (10), moracin M (11) and kuwanon G (12). Among these, 2,4,3′-trihydroxydihydrostilbene (7) is isolated for the first time from Morus alba and constitutes a novel potent tyrosinase inhibitor (IC50 0.8 ± 0.15). We report here for the first time dihydrooxyresveratrol (5) as a potent natural tyrosinase inhibitor (IC50 0.3 ± 0.05). Computational docking analysis indicated the binding modes of six tyrosinase inhibitors with the aminoacids of the active centre of tyrosinase. Finally, we found both MAM extract and compounds 1, 6 and 7 to significantly suppress in vivo melanogenesis during zebrafish embryogenesis.

Highlights

The degree and distribution of melanin pigmentation are the main regulators of the mammalian skin and hair color [1]
In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme, as it catalyzes the rate-limiting steps in mammalian melanogenesis
Screening for tyrosinase inhibition properties of all extracts was performed using an initial concentration of 300 μg/mL and this revealed 99 extracts with weak tyrosinase inhibitory properties (20%–40% inhibition), 41 extracts with moderate (40%–70% inhibition), and 15 extracts with promising anti-melanogenic potential (Supplementary Material Table S1)

Summary

Introduction

The degree and distribution of melanin pigmentation are the main regulators of the mammalian skin and hair color [1]. Tyrosinase catalyzes the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) (monophenolase activity) and the subsequent oxidation of this o-diphenol to the corresponding quinone, dopaquinone (diphenolase activity) From this point on, melanin is formed by a combination of enzymatically catalyzed and chemical reactions [2]. Natural occurring compounds have received wide acceptance, whole plant extracts have often demonstrated better or broader skin protective properties due to their complex composition [9]. Beyond these applications, tyrosinase inhibitors constitute an emerging area in the food industry, as they are used to prevent enzymatic browning in fruits and vegetables

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