日本香粧品学会誌

Vol. 44, No. 4, pp. 283–288（2020）〈Regular Article〉

A Potential of α-Tocopherol Fatty Acid Ester as an Anti-Pigmentation AgentKarin ENDO1, Suzuna OSAWA1, Taeko MIZUTANI1, Yuto MIYAGUCHI2,Yuri OKANO1, Hitoshi MASAKI1, *(Accepted: September 24, 2020)

Abstract
Solar lentigos (SLs) are pigmented spots that typically appear in photoaged skin depending on its solar exposure history.
It has been reported that ultraviolet (UV) light is a major cause of SLs because UV is a strong promoter of reactive oxygenspecies (ROS). The process of skin pigmentation has been demonstrated to be divided into three major steps: melanocyte
proliferation, the maturation of melanosomes (MSs) according to increases in melanin synthesis and the transfer of MSs
to keratinocytes. The maturation of MSs and their transfer from melanocytes to keratinocytes following UV exposure areaccelerated via the eﬀects of soluble factors such as α-melanocyte stimulating hormone, endothelin-1, stem cell factor andprostaglandin E2 (PGE2), produced by UV-exposed keratinocytes in autocrine and paracrine fashions. Among those soluble
factors, PGE2, which is synthesized by keratinocytes in response to UV exposure, has been reported to promote dendrite
development and melanin synthesis of melanocytes. The purpose of this study was to characterize the potential anti-pigmentation eﬀects of α-tocopherol fatty acid ester (VE-FA), which was synthesized with a natural fatty acid mixture enriched withlinoleic acid, focusing on the activation of melanocytes and acceleration of MS incorporation to keratinocytes by the conditioned medium of UVB-exposed keratinocytes. VE-FA suppressed the incorporation of ﬂuorescent beads, which were usedas pseudo-MSs, into keratinocytes treated with the conditioned medium (CM) from UVB-exposed keratinocytes. In addition,
treatment with VE-FA abolished the increased proliferation and dendrite elongation of melanocytes treated with CM fromkeratinocytes exposed to UVB. Furthermore, VE-FA reduced the level of PGE2 in the CM from keratinocytes exposed toUVB. In summary, the results of this study demonstrated the possibility that VE-FA has an anti-pigmentation eﬀect throughits suppression of MS transfer to keratinocytes and of melanocyte activation following UVB exposure.
Key words: UVB, ROS, melanosome transfer, prostaglandin E2.
1.

Introduction

Solar lentigos (SLs) appear on the skin depending on its
solar exposure history and are recognized as a typical symptom of photoaged skin. Ultraviolet (UV) radiation in solar
light is the major inducer of skin pigmentation, and also has
been well recognized as a major generation source of reactive
oxygen species (ROS). The role of ROS on skin pigmentation has been well studied. For example, prostaglandin E2(PGE2), which is produced by keratinocytes in response to
ROS or to UV exposure, has been characterized for its actions
to aﬀect skin pigmentation such as inducing the developmentof dendrites and stimulating melanin synthesis of melanocytes1, 2). In general, the process of skin pigmentation has been
demonstrated to be divided into three major steps: the proliferation of melanocytes, the increase of melanin synthesis inmelanosomes (MSs) of melanocytes and the transfer of MSs
to neighboring keratinocytes3, 4). In fact, it has been reported
that PGE2 also stimulates the secretion of mature MSs from1

Tokyo University of Technology, School of Bioscience and Biotechnology (1404–1 Katakura-machi, Hachioji-shi, Tokyo 192–0982, Japan)
2MITSUBISHI-CHEMICAL FOODS CORPORATION* Corresponding author: Tokyo University of Technology, School ofBioscience and Biotechnology, 1404–1 Katakura-machi, Hachiojishi, Tokyo 192–0982, Japan (E-mail: masaki@stf.teu.ac.jp)

melanocytes and increases the incorporation of those MSs
into surrounding keratinocytes5). Gathering these facts, theinvolvement of ROS generated by UV exposure in regulating
the process of skin pigmentation is strongly suggested, and it
is considered that antioxidants are major candidates for antipigmentation agents.
Indeed, ascorbic acid (vitamin C, VC), which is a typical antioxidant, and its derivatives, are widely used as antipigmentation agents to prevent or improve pigmented spots
on the skin such as SLs6). On the other hand, althoughα-tocopherol (vitamin E, VE), a type of lipophilic vitamin,
and its derivatives are mainly formulated in foods and cosmetics in order to maintain the stability of those productsfrom oxidation, they are not expected to have physiologicaleﬀects including anti-pigmentation eﬀects in spite of theirantioxidant properties. In a previous study, we reported that
α-tocopherol increases the level of intracellular glutathione byupregulating the level of mRNA encoding γ-glutamylcysteinesynthetase (γ-GCS), which is a rate limiting enzyme of