Melanogenesis inhibition of β-lapachone, a natural product from Tabebuia avellanedae, with effective in vivo lightening potency

Abstract

β-Lapachone is an ortho naphthoquinone obtained from the bark of the lapacho tree (Tabebuia avellanedae), which has been used medicinally for centuries. The purpose of this study was to investigate the effects of β-lapachone on inhibitory mechanism of melanogenesis. β-Lapachone inhibited melanin synthesis and tyrosinase activity at 0.8 μM in melan-a cells. Also, β-lapachone reduced the expression of tyrosinase and tyrosinase-related protein-1 at transcriptional and translational levels. The decreased expression of tyrosinase and tyrosinase-related protein-1 might result from the reduced microphthalmia-associated transcription factor (MITF) level which regulates major melanogenic proteins. The reduced level of MITF was associated with delayed ERK activation by β-lapachone. Furthermore, β-lapachone reduced melanogenesis in the human 3D skin tissue culture; besides, it dramatically inhibited body pigmentation of zebrafish and decreased melanin content and tyrosinase activity. These results show that β-lapachone may be useful as a potential depigmentation agent for various hyperpigmentation disorders.

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

“…Thus, further evaluation explained that sesamol inhibited melanogenesis in melan-a cells via p38 MAPK and JNK pathway [63]. On the other hand, β-Lapachone of Tabebuia avellanedae at concentration of 0.8 μM remarkably inhibited melanin synthesis and TYR activity in zebrafish embryo which led to its pale phenotypic body pigmentation [64]. The depigmentation in zebrafish embryos can be further explained by reduced expression of TYR and TRP-1 at transcriptional gene and translational protein levels in melan-a cells [64].…”

“…On the other hand, β-Lapachone of Tabebuia avellanedae at concentration of 0.8 μM remarkably inhibited melanin synthesis and TYR activity in zebrafish embryo which led to its pale phenotypic body pigmentation [64]. The depigmentation in zebrafish embryos can be further explained by reduced expression of TYR and TRP-1 at transcriptional gene and translational protein levels in melan-a cells [64]. The decreased level of MITF was coupled with delayed activation of extracellular signal-regulated kinase (ERK) by β-lapachone treatment [64,65].…”

“…The depigmentation in zebrafish embryos can be further explained by reduced expression of TYR and TRP-1 at transcriptional gene and translational protein levels in melan-a cells [64]. The decreased level of MITF was coupled with delayed activation of extracellular signal-regulated kinase (ERK) by β-lapachone treatment [64,65]. Activation and acceleration of the degradation of ERK has a significant effect on MITF expression [54,65].…”

“…Activation and acceleration of the degradation of ERK has a significant effect on MITF expression [54,65]. Furthermore, β-lapachone reduced melanogenesis in the reconstituted 3D human skin tissue culture, MelanoDermTM (MEL-300-B, MatTek Corporation, Ashland, USA) as indicated by brightness value (L*) within 2–3 weeks [64]. …”

Obtenção de extratos padronizados em ácido clorogênico, rutina e isoquercitrina a partir das folhas de Morus nigra L. : inibição de tirosinase e citotoxicidade

“…Encontrada em bactérias, fungos, plantas e animais, a melanina é um dos pigmentos mais amplamente distribuídos na natureza (36), que determina a cor da pele humana, cabelos e olhos (35). A principal função da melanina é a proteção contra radiação ultravioleta (UV) (37).…”