Zebrafish as a new model for phenotype‐based screening of melanogenic regulatory compounds

Abstract

Although many hypo-pigmenting agents are currently available, the demand for novel whitening agents is increasing, in part due to the weak effectiveness and unwanted side effects of currently available compounds. To screen for novel hypo-pigmenting agents, many methodologies such as cell culture and enzymatic assays are routinely used. However, these models have disadvantages in terms of physiological and economic relevance. In this study, we validated zebrafish as a whole-animal model for phenotype-based screening of melanogenic inhibitors or stimulators. We used both the well-known melanogenic inhibitors (1-phenyl-2-thiourea, arbutin, kojic acid, 2-mercaptobenzothiazole) and newly developed small molecule compounds (haginin, YT16i). All the tested compounds produced inhibitory effects on the pigmentation of zebrafish, most likely due to their inhibitory potential on tyrosinase activity. In simultaneous in vivo toxicity tests, a newly developed melanogenic inhibitor YT16i showed massive abnormalities in terms of deformed morphologies and cardiac function. Together, these results provide a rationale in screening and evaluating the putative melanogenic regulatory compounds. We suggest that the zebrafish system is a novel alternative to mammalian models, with several advantages including the rapidity, cost-effectiveness, and physiological relevance.

Imiquimod induces apoptosis of human melanocytes

“…To conWrm this inhibitory eVect of imiquimod in in vivo, we used zebraWsh model system as it is a novel alternative to mammalian model with the advantages of physiological relevance [3]. As shown in Fig.…”

Whitening Effects of MarinePseudomonasExtract

“…Image analysis showed a significant decrease in the ratio of PA/EA in the treated skin (88±47.5), as compared to that of the control skin (227±36.6). The Zebrafish model system is a novel alternative to mammalian models with the advantages of physiological relevance 6 . The marine bacterial methylene chloride extract also produced remarkable inhibition on the body pigmentation of zebrafish (Fig.…”

Methanol Partition Fraction of Ethanol Extract of Discorea nipponica Makino Inhibits Melanogenesis

“…Zebrafish is a well-known vertebrate model system in many research fields and has been established as a new in vivo model for evaluating the antimelanogenic activity of melanogenic regulatory compounds [14]. This animal model system has several advantages, including easy maintenance and handling of the animals and high efficiency of drug penetration through the skin.…”

“…Evaluation of melanogenesis inhibitory activity in a zebrafish model system was done according to the procedure of Choi et al [14] as modified by Lin [15]. Adult zebrafish were obtained from a commercial dealer and kept in acrylic tanks with a 14 h/10 h light/dark cycle at 28 °C.…”