Cargando…

The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Jinpeng, Yang, Ying, Jia, Bingyi, Li, Siqi, Zhang, Ximei, Gao, Rongyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649847/
https://www.ncbi.nlm.nih.gov/pubmed/34887767
http://dx.doi.org/10.3389/fphar.2021.783730
_version_ 1784611085687455744
author Lv, Jinpeng
Yang, Ying
Jia, Bingyi
Li, Siqi
Zhang, Ximei
Gao, Rongyin
author_facet Lv, Jinpeng
Yang, Ying
Jia, Bingyi
Li, Siqi
Zhang, Ximei
Gao, Rongyin
author_sort Lv, Jinpeng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8649847
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86498472021-12-08 The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation Lv, Jinpeng Yang, Ying Jia, Bingyi Li, Siqi Zhang, Ximei Gao, Rongyin Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8649847/ /pubmed/34887767 http://dx.doi.org/10.3389/fphar.2021.783730 Text en Copyright © 2021 Lv, Yang, Jia, Li, Zhang and Gao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lv, Jinpeng
Yang, Ying
Jia, Bingyi
Li, Siqi
Zhang, Ximei
Gao, Rongyin
The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title_full The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title_fullStr The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title_full_unstemmed The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title_short The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
title_sort inhibitory effect of curcumin derivative j147 on melanogenesis and melanosome transport by facilitating erk-mediated mitf degradation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649847/
https://www.ncbi.nlm.nih.gov/pubmed/34887767
http://dx.doi.org/10.3389/fphar.2021.783730
work_keys_str_mv AT lvjinpeng theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT yangying theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT jiabingyi theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT lisiqi theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT zhangximei theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT gaorongyin theinhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT lvjinpeng inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT yangying inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT jiabingyi inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT lisiqi inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT zhangximei inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation
AT gaorongyin inhibitoryeffectofcurcuminderivativej147onmelanogenesisandmelanosometransportbyfacilitatingerkmediatedmitfdegradation