Detection of Raspberry Ketone after Percutaneous Absorption of Rhododendrol-Containing Cosmetics and Its Mechanism of Formation

Lihao Gu,Kazuhisa Maeda,Akio Fujisawa

doi:10.3390/cosmetics8040097

Abstract

Here, we aimed to elucidate the mechanism of rhododendrol (RD)-induced leukoderma. We investigated the skin permeability of RD in an aqueous solution and in different cosmetic formulations (lotion and emulsion) in an in vitro skin permeation study. The samples were analyzed using high-performance liquid chromatography (HPLC), and an unknown substance appeared on the spectrum. For identification, we analyzed various possible substances, such as raspberry ketone (RK) and rhododendrol quinone, using HPLC and then compared the detected absorption spectra and further verified the matched components using liquid chromatography–mass spectrometry. The unknown substance was found to be RK. To clarify the mechanism of formation of RK, we conducted a 24-h skin permeation test on heat-treated skin. By quantifying the RK in the samples using HPLC, we observed that an enzyme in the skin seemed to be the cause of RK generation and that the components of the emulsion formulation could also be a cause. To investigate the enzyme, we reacted alcohol dehydrogenase with RD and observed that it was one of the converting enzymes. As RK has been reported to be a substance that causes leukoderma, the intraepidermal metabolism of RD to RK may be one of the mechanisms of susceptibility to leukoderma.

Highlights

Because bright skin looks cleaner, and for other reasons, East Asian countries have tried since ancient times to make their skin brighter
Brightening cosmetics are becoming more popular. Epidermal depigmentation products, such as brightening cosmetics, are typed according to their modes of action, which include promoting the excretion of melanin, melanin breakdown, inhibiting melanocyte activity, and inhibiting melanin synthesis by inhibiting tyrosinase, a key enzyme in the melanosome formation pathway [1]
Among products that inhibit tyrosinase, cosmetics containing 2% 4-(p-hydroxyphenyl)2-butanol or rhododendrol (RD), which was developed in 2008 as an active ingredient of quasi-drugs, were voluntarily recalled after leukoderma was confirmed in consumers who had used them

Summary

Introduction

Because bright skin looks cleaner, and for other reasons, East Asian countries have tried since ancient times to make their skin brighter. Epidermal depigmentation products, such as brightening cosmetics, are typed according to their modes of action, which include promoting the excretion of melanin, melanin breakdown, inhibiting melanocyte activity, and inhibiting melanin synthesis by inhibiting tyrosinase, a key enzyme in the melanosome formation pathway [1]. Among products that inhibit tyrosinase, cosmetics containing 2% 4-(p-hydroxyphenyl)2-butanol or rhododendrol (RD), which was developed in 2008 as an active ingredient of quasi-drugs, were voluntarily recalled after leukoderma was confirmed in consumers who had used them. As of November 2016, there were 19,605 confirmed cases of leukoderma. Most of these patients have recovered, but some still suffer from the disease even after 3 years [2]

Objectives

Results

Conclusion