Abstract
The therapeutic use of curcumin and chemically modified curcumin (CMC) for suppressing melanogenesis and tyrosinase activity have been recognized. J147 is a modified version of curcumin with superior bioavailability and stability. However, there is no report about the effects of J147 on pigmentation in vitro and in vivo. In our studies, we investigated the hypopigmentary effects of J147 treatment on melanocytes and explored the underlying mechanism. The present studies suggested that J147 suppressed both basal and α-MSH-induced melanogenesis, as well as decreased melanocyte dendricity extension and melanosome transport. J147 played these roles mainly by activating the extracellular signal-regulated protein kinase (ERK) pathway. Once activated, it resulted in MITF degradation and further down-regulated the expression of tyrosinase, TRP-1, TRP-2, Myosin Va, Rab27a and Cdc42, ultimately inhibited melanin synthesis and melanosome transport. Furthermore, the hypopigmentary effects of J147 were demonstrated in vivo in a zebrafish model and UVB-induced hyperpigmentation model in brown guinea pigs. Our findings also suggested that J147 exhibited no cytotoxicity in vitro and in vivo. Taken together, these data confirmed that J147 may prove quite useful as a safer natural skin-whitening agent.
Highlights
Skin pigmentation depends on both melanin synthesis and distribution in the epidermis layer
J147 is developed as a potent compound of curcumin derivative with greater stability and bioavailability (Li et al, 2020)
We examined the influence of J147 on melanin synthesis
Summary
Skin pigmentation depends on both melanin synthesis and distribution in the epidermis layer. Melanosomes migrated along microtubules and actin filaments to the dendrite tips of the cells and to the neighboring keratinocytes to finish the distribution process (Beaumont et al, 2011; Ohbayashi and Fukuda, 2012). Melanin protects human skin from ultraviolet (UV) damage, toxic chemicals and other environmental factors (Slominski et al, 2004; Yousaf et al, 2020). Excessive production and accumulation induces hyperpigmentation and is associated with skin disorders like post-inflammatory melanoderma, melasma and solar lentigines, leading to remarkable psychosocial burden (Pillaiyar et al, 2017). It is necessary to develop effective and safe skin whitening agents
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