Depigmentation Effect of Kadsuralignan F on Melan-A Murine Melanocytes and Human Skin Equivalents

Myeong-Jin Goh,Jun-Cheol Cho,De-Yun Kong,Quan-Quan He,Liang Cheng,Hae-Kwang Lee,Yong Na,Jae-Ho Yeon

doi:10.3390/ijms14011655

Abstract

The development of melanogenic inhibitors is important for the prevention of hyperpigmentation, and, recently, consideration has been given to natural materials or traditionally used ingredients such as Chinese medicine. The aim of this study is the evaluation of a new anti-melanogenic candidate, kadsuralignan F, from the natural plant Kadsura coccinea, as well as the determination of mechanisms of melanogenesis inhibition at a molecular level. Kadsuralignan F significantly reduced melanin synthesis in a dose-dependent manner in a murine melanocyte cell line and human skin equivalents. There was no direct inhibition on mushroom tyrosinase or cell-extract tyrosinase activity, and mRNA expression of tyrosinase and other melanogenic genes such as tyrosinase-related protein-1 (trp-1) or trp-2 were not affected by kadsuralignan F. Interestingly, the protein level of tyrosinase was dramatically downregulated with kadsuralignan F treatment. We found that a decrease of tyrosinase protein by kadsuralignan F was fully recovered by MG132, a proteasome inhibitor, but not by chloroquine, a lysosome inhibitor. In this study, we found that kadsuralignan F, a lignan from an extract of Kadsura coccinea, has an inhibitory activity on melanin synthesis through tyrosinase degradation. These findings suggest that kadsuralignan F can be used as an active ingredient for hyperpigmentation treatment.

Highlights

Melanin synthesis and distribution contributes to mammalian skin color [1]
Melan-A cells were cultured for three days at the indicated concentrations of kadsuralignan F, and cell viability was assessed by WST-1 assay (Figure 2)
The amount of the microphthalmia-associated transcription factor (MITF) protein changes were expected to be low impact, and it was confirmed as a result of the Western blot experiment. These results suggest that melanin synthesis inhibition by kadsuralignan F did not result from the decrease of gene expression of melanogenic proteins, but was affected by the decrease in the expression level of tyrosinase protein, which might be related to post-translational modification processes of tyrosinase in melanocytes

Summary

Introduction

Melanin synthesis and distribution contributes to mammalian skin color [1]. Melanin pigments have a role in the protection of skin from ultraviolet irradiation, as well as various oxidative stresses [2].irregular synthesis of melanin may cause problems with the skin, and there are a number of hyperpigmentary disorders or conditions attributed to this, such as melasma, solar lentigo, post-inflammatory hyperpigmentation, or freckles [3]. Melanin synthesis and distribution contributes to mammalian skin color [1]. Melanin pigments have a role in the protection of skin from ultraviolet irradiation, as well as various oxidative stresses [2]. Irregular synthesis of melanin may cause problems with the skin, and there are a number of hyperpigmentary disorders or conditions attributed to this, such as melasma, solar lentigo, post-inflammatory hyperpigmentation, or freckles [3]. Melanin is synthesized in the melanosome, a unique organelle in melanocytes [4]. There are three types of melanogenic enzymes in the melanosome: tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2. It is well known that tyrosinase, a type I membrane glycoprotein, plays the most critical role in melanin synthesis [5]. Tyrosinase participates in the critical rate-limiting step in melanin synthesis

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Conclusion