A Zebrafish Embryo as an Animal Model for the Treatment of Hyperpigmentation in Cosmetic Dermatology Medicine

Abstract

For years, clinical studies involving human volunteers and several known pre-clinical in vivo models (i.e., mice, guinea pigs) have demonstrated their reliability in evaluating the effectiveness of a number of depigmenting agents. Although these models have great advantages, they also suffer from several drawbacks, especially involving ethical issues regarding experimentation. At present, a new depigmenting model using zebrafish has been proposed and demonstrated. The application of this model for screening and studying the depigmenting activity of many bioactive compounds has been given great attention in genetics, medicinal chemistry and even the cosmetic industry. Depigmenting studies using this model have been recognized as noteworthy approaches to investigating the antimelanogenic activity of bioactive compounds in vivo. This article details the current knowledge of zebrafish pigmentation and its reliability as a model for the screening and development of depigmenting agents. Several methods to quantify the antimelanogenic activity of bioactive compounds in this model, such as phenotype-based screening, melanin content, tyrosinase inhibitory activity, other related proteins and transcription genes, are reviewed. Depigmenting activity of several bioactive compounds which have been reported towards this model are compared in terms of their molecular structure and possible mode of actions. This includes patented materials with regard to the application of zebrafish as a depigmenting model, in order to give an insight of its intellectual value. At the end of this article, some limitations are highlighted and several recommendations are suggested for improvement of future studies.

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

“…PTU was used to suppress melanogenesis in zebrafish without adverse toxicity [76,77]. IBMX was used as better melanogenic inducer agent in zebrafish model instead of α-MSH to mimic cAMP signaling pathway in melanogenesis omitting any effects of α-MSH towards zebrafish [30,78]. Inhibition of melanin by FLA and FLB in 0.1% DMSO was observed every 48 h until 144 hpf.…”

“…On the contrary, zebrafish (Danio rerio) model has been identified as an ideal model organism for large screening due to their smaller in size, easy to maintain, readily reproducible in laboratories, externally and rapidly developing transparent embryos permitting live observations with high throughput chemical screening [26]. The zebrafish model has also been extensively used as a resort to toxicity assessment of drug compounds [27][28][29] and melanogenesis studies since the lower vertebrate is highly comparable to human melanogenesis [30]. The presence of melanin pigments on surface of zebrafish larvae allow ready observation in testing percutaneous effect of depigmenting agents [31].…”

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Kit responds to SCF binding by inducing PI3kinase and MAPK cascades. Therefore, the ability of diosmetin (C 16 H 12 O 6 ), Glechoma hederacea extract, Withania somnifera extract, astaxanthin (C 40 H 52 O 4 ), and glyceollins (C 20 H 18 O 5 ) of Chrysanthemum morifolium to block c‐Kit signaling and prevent pigment formation is via inhibition of melanoblast differentiation and regulating the expression of melanogenic genes and proteins rather than simply by inhibiting the TYR expression …”

GSK-3β-Targeting Fisetin Promotes Melanogenesis in B16F10 Melanoma Cells and Zebrafish Larvae through β-Catenin Activation

“…Especially, TPA at below 85 nM identically stimulated melanogenesis regardless of cell types such as mouse B16F10 melanoma cells and human normal melanocytes, which indicates that B16F10 cells are a sensitive melanogenesis model. Along with B16F10 melanoma cells, zebrafish larvae have been used as an attractive in vivo model for melanogenesis because the zebrafish model directly displays melanin strips, which can be visualized by the naked eye [25][26][27]. Zebrafish also shared genetic similarity with mouse and human during pigment expression from the neural crest-derived stem cells to melanocyte progenitor by activating MITF, TYRP-1, DCT, and tyrosinase [28,29].…”