Introduction
Vitiligo is an acquired chronic depigment disorder of the skin resulting
from the selective destruction of melanocytes (Boniface, Seneschal,
Picardo & Taieb, 2018; Ezzedine, Eleftheriadou, Whitton & van, 2015;
Picardo et al., 2015). It is a high morbidity disease that equally
affects adults and children of both sexes. Vitiligo is prevalent in
0.51% of the world’s population; however, in some countries, this
number is significantly higher: 8.8% (India) and 4% (Mexico)
(Boisseau-Garsaud, Garsaud, Cales-Quist, Helenon, Queneherve & Claire,
2000; Ezzedine et al., 2012; Sehgal & Srivastava, 2007). Vitiligo is
primarily classified as non-segmental vitiligo and segmental vitiligo.
Non-segmental vitiligo, which is characterized by symmetrical and
bilateral white patches, is the most common form of this disease;
segmental vitiligo is considerably less common and usually has a
unilateral distribution.
Although vitiligo is not a fatal disease, it is associated with
considerable negative social effects among patients, especially women
and children (Elbuluk & Ezzedine, 2017; Olsen, Gallacher, Finlay,
Piguet, & Francis, 2016; Anonymous, 2015). Therefore, research on
effective treatment of vitiligo has never stopped; interventions
developed for vitiligo include topical therapies, phototherapy
therapies, herbal medicine, surgical treatments, and psychological
treatments. Medications such as glucocorticosteroids, calcineurin
inhibitors, melagenina, vitamin D, and Janus kinase inhibitors have been
employed for improving the symptoms of vitiligo. Unfortunately, the
outcomes of the aforementioned treatments vary among individuals, and
they are often unsatisfactory; furthermore, treatment is more efficient
in recently developed lesions than in older lesions (Hayashi et al.,
2016; Lopes, Trevisani, Trevisani, Trevisani, Melnik & Melnik, 2016;
Cohen, Elbuluk, Mu & Orlow, 2015; Niezgoda et al., 2017). Therefore,
there is a need for the development of treatment strategies for
vitiligo, including the identification of new anti-vitiligo
chemotherapeutic agents (Rashighi & Harris, 2017; Rodrigues, Ezzedine,
Hamzavi, Pandya & Harris, 2017).
Previous studies have discussed the role of the Wnt/β -catenin
signalling pathway in the development of melanocytes (Li et al., 2019;
Yamada et al., 2013). Wnt/β -catenin, a highly conserved
signalling pathway, is important for development, particularly,
embryonic development. Aberrant Wnt signalling is involved in many
diseases (Clevers & Nusse, 2012; Zeng et al., 2005; Zimmerman, Moon &
Chien, 2012). Previous studies have suggested that regulation of Wnt
could be used to treat vitiligo through modulation of melanocyte
functions, and appropriate Wnt agonists may play an effective role in
curing vitiligo. However, perhaps because of the lack of effective and
Wnt-specific agonists for medical applications, the effect of
Wnt-specific small-molecule agonists on vitiligo have not been proven
thus far.
Our previous research identified a new series of phenanthridine-specific
agonists of the Wnt/β -catenin signalling pathway (Wang et al.,
2013; Chen et al., 2018; Chen et al., 2016; Chen et al., 2019). In
consideration of the role of Wnt in melanogenesis, it is worth
discussing whether appropriate, potent phenanthridine Wnt agonists have
the potential to cure or improve the symptoms of vitiligo. Therefore, in
this study, we designed new phenanthridine derivatives and evaluated
their anti-vitiligo effects in vitro and in vivo. Furthermore, we
revealed an efficient regulatory network underlying melanin biosynthesis
and a related target protein. These results suggest a promising
therapeutic strategy for vitiligo and the potential applications of
phenanthridine derivatives in the treatment of vitiligo.