Abstract
Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis.
Highlights
As a dark pigment present in skin, hair, eyes, and other tissues, melanin contributes to human appearance and to skin homeostasis [1]
When compared to the carbon and proton values in luteolin, the same pattern was seen in luteolin 7-sulfate and the downfield carbon data for C-6 and C-8, as well as the significantly downfield chemical shifts of H-6 and H-8 strongly indicating the presence of an electron withdrawing sulfate group at position C-7
The current study showed that luteolin 7-sulfate attenuated both the activity and level protein in cells stimulated by either α-melanocyte-stimulating hormone (α-MSH)
Summary
As a dark pigment present in skin, hair, eyes, and other tissues, melanin contributes to human appearance and to skin homeostasis [1]. A variety of factors like hormonal changes and nutritional status affect skin melanin synthesis, and hypo- or hyper-pigmentation can be caused by the disruptions in melanogenesis [2]. Freckles, and senile lentigines result from an uneven distribution or abnormal accumulation of melanin in the skin, and such pigmentation patterns are sometimes undesired by many people pursuing aesthetic ideals. Melanin synthesis is directed by microphthalmia-associated transcription factor (MITF) [3]. MITF is activated in response to external stimuli by multiple mechanisms, including cAMP-responsive element binding protein (CREB), Wnt, glycogen synthase kinase 3β, and mitogen activated protein kinases, and in turn modulates the expression of melanogenic enzymes such as tyrosinase (TYR). TYR catalyzes the oxidation of L-tyrosine or L-3,4-dihydroxyphenylalanine (L-DOPA) to DOPA-quinone, Antioxidants 2019, 8, 87; doi:10.3390/antiox8040087 www.mdpi.com/journal/antioxidants
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