Hesperidin, A Popular Antioxidant Inhibits Melanogenesis via Erk1/2 Mediated MITF Degradation.

Heun Lee,Sung Chang,Woo Lee,Ga-Young Lee

doi:10.3390/ijms160818384

Abstract

Regulation of melanogenesis has been the focus of treatment for hyperpigmentary skin disorders. Although hesperidin is one of the most well-known, naturally occurring flavonoids with antioxidant and anti-inflammatory effect, its anti-melanogenic effect is not known. The present study aims to determine the anti-melanogenic effect of hespiridin as well as its underlying molecular mechanisms. Melanin contents were measured in normal human melanocytes and B16F10 melanoma cells. Protein and mRNA levels of tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1) and TRP-2 were determined. Melanogenesis-regulating signals were examined. In results, hesperidin strongly inhibited melanin synthesis and tyrosinase activity. Hesperidin decreased tyrosinase, TRP-1, and TRP-2 protein expression but increased phospho-extracellular signal-regulated kinase 1/2 (p-Erk1/2) expression. Specific inhibitor of Erk1/2 or proteasome inhibitor reversed the inhibition of melanogenesis induced by hesperidin. Taken together, hesperidin, a popular antioxidant, stimulated Erk1/2 phosphorylation which subsequently degraded MITF which resulted in suppression of melanogenic enzymes and melanin synthesis.

Highlights

IntroductionThe pigment produced by melanocytes, forms the color of human skin and hair
Melanin, the pigment produced by melanocytes, forms the color of human skin and hair
Treatment with hesperidin at concentration ranging from 0.1–40 μM had no cytotoxic effect on normal human melanocytes (Figure 1a) and B16F10 cells (Figure 1b)

Summary

Introduction

The pigment produced by melanocytes, forms the color of human skin and hair. Melanin is transferred to keratinocytes to protect nucleus of keratinocyte against DNA damage by ultraviolet (UV). Melanin has an important protective role, overproduction and accumulation of melanin could cause hyperpigmentary disorders such as melasma, solar lentigo, and post-inflammatory hyperpigmentation. Regulation of melanogenesis has been the focus of treatment for hyperpigmentary skin disorders and exploration of skin whitening agents [1,2]. Melanogenesis is a complex process with different stages involving various enzymes [2]. Tyrosinase, the key enzyme of melanogenesis, is involved in rate-limiting step for melanin synthesis. MITF is regulated through various signal pathways such as cAMP mediated pathway, MEK/extracellular signal-regulated kinase 1/2 (Erk1/2) pathway, phosphatidylinositol 3 kinase (PI3K)/Akt pathway, and Wnt signaling pathway at transcriptional or post-translational level [3]

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