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.