日本香粧品学会誌–8（2017）Vol. Stimulation
41, No. 1, pp.
of 1Noggin
Signaling in Keratinocytes by an Extract of Mulberry (Morus alba L)

1〈Regular Article〉

Stimulation of Noggin Signaling in Keratinocytes
by an Extract of Mulberry (Morus alba L)
Hiroyuki YAMABA1,*, Hiroaki ADACHI1, Hiroshi TANAKA1,
Satoru NAKATA1, Chaogang WANG2, Katsutoshi YOSHIZATO3,4(Accepted: November 30, 2016)

Abstract
Traditional Chinese medicine has utilized various parts of Morus alba L (white mulberry) to ameliorate chronic sicknesses caused by organ or tissue disorders. We investigated the effects of the ethanol extract of mulberry fruits on the expression of the hair cycle-associated genes of cultured human keratinocytes to explore its potential as a hair-nourishment ingredient. Two types of cultured human cells were utilized: human epidermal keratinocytes (HEKs) and HaCaT cells (a cell line ofkeratinocyte). Cells were treated with mulberry extracts and its effects were evaluated in terms of growth capacity and theexpression of 12 known hair cycle-associated genes. Mulberry extracts signiﬁcantly stimulated the growth of HEKs andHaCaT cells. Among the 12 tested genes of HaCaT cells, the expression of noggin gene (NOG) was increased most prominently by the extract. The up-regulated expression of NOG induced by the extract was also observed in HEKs. In contrast,
the expression of bone morphogenetic protein 4 gene (BMP4) and p27Kip1 gene, both genes associated with noggin signaling,
was down-regulated in HaCaT cells by the extract, strongly suggesting that the extract may have stimulated keratinocyte
growth through the suppressive effects of noggin on BMP-p27Kip1 signaling. Furthermore, HaCaT cells were exposed to oxidative stress using t-butylhydroperoxide or UV and then treated with the extract in order to determine whether the extract
mitigates oxidative stress-induced alterations. HaCaT cells signiﬁcantly decreased the NOG expression when exposed to oxidative stress. The extract was able to recover the oxidative stress-induced suppression of NOG. These results suggest thatmulberry extracts mitigate oxidative stress-induced damage in cells. Therefore the results in this study suggest the potentialof the mulberry extracts as an ingredient in hair-nourishment products.
Key words:

1.

Morus alba L, hair growth, keratinocytes, noggin, oxidative stress.

Introduction

Morus alba L is a species of Moru in the family of Moraceae, and is commonly known as white mulberry (mulberry inthis study). Its fruits have been utilized as crude drugs fornourishment, robustness, relief from anemia, and hairgrowth1). These fruits contain large amounts of polyphenols
including apigenin, luteolin, and quercetin2), which exhibit
stronger anti-oxidative activities than those of other Moraceae
species such as M. nigra and M. laevigata3). Although themulberry fruit extract has been conventionally utilized as amaterial that has the ability to stimulate hair growth, few studies have examined the mechanistic aspects underlying theireffects on hair growth-related compromises.
Terminal hairs retain their growth capacity throughout life
in a unique manner; they undergo cycles of growth and regression involving the reproduction of new (secondary) hairs
and their active growth (anagen), the apoptotic involution of
hair follicles (catagen), and relative resting of dermal papillain the quiescence and shedding of hairs (telogen-exogen). The
transitions from telogen to anagen and from anagen to catagen*Corresponding author
1

Research Laboratories, Nippon Menard Cosmetic Co., Ltd. (2–7 Torimi-cho, Nishi-ku, Nagoya 451–0071, Japan)
E-mail: yamaba.hiroyuki@menard.co.jp

are physiologically, pathologically, and also clinically important because the duration of anagen has been directly related
to the thickness and length of hair growth4).
Hair follicles (HFs) are exposed to numerous growth stimulatory and inhibitory factors, and a tightly controlled balance
between these two factors causes HFs to transit between thedistinct hair cycle stages4). Although the components of thisnetwork have not yet been completely revealed, bone morphogenetic protein (BMP)5) and Wnt/β-catenin6) signals havebeen suggested as major players in this network; BMP signals
may function as a growth inhibitory factor (catagen promoter)in contrast to Wnt/β-catenin signals, which act as growth
stimulatory factors (anagen promoters). BMP expression isabsent in early anagen and gradually intensiﬁes to reach its
peak level in anagen. BMP expression remains high in catagen, but becomes absent in telogen7). Noggin is an antagonistof BMP signaling8), a major inhibitory regulator of HF cycling9). Noggin expression remains high in anagen and declines in catagen7). Delivery of extraneous noggin by intracutaneous implantation of noggin-soaked beads was able to decrease BMP signaling activity and initiate anagen10). BMP and2Beijing Bosye Hair Research Center, Beijing, China
Osaka City University Graduate School of Medicine, Synthetic Biology Laboratory, Osaka, Japan
4
Phoenixbio. Co., Ltd., Higashihiroshima, Hiroshima, Japan
3