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Kazinol U inhibits melanogenesis through the inhibition of tyrosinase-related proteins via AMP kinase activation.
- Source :
- British Journal of Pharmacology; Mar2019, Vol. 176 Issue 5, p737-750, 14p, 8 Graphs
- Publication Year :
- 2019
-
Abstract
- <bold>Background and Purpose: </bold>Kazinol U is a prenylated flavan isolated from an extract of Broussonetia kazinoki Sieb (Moraceae). Kazinol U has shown cytoprotective effects against cytokine-induced apoptotic cell death and induces AMP kinase (AMPK) activation through LKB1 activation. However, kazinol U has not been tested as a regulator of melanogenesis, although bark extract of B. kazinoki has been used as a cosmetic ingredient for skin conditioning.<bold>Experimental Approach: </bold>We cultured mouse, human melanoma cells and normal human melanocytes to demonstrate anti-melanogenic effects of kazinol U. A tyrosinase activity assay, Western blot, RT-qPCR and a luciferase reporter gene assay were performed to determine the anti-melanogenic mechanisms of kazinol U. We confirmed its effect on melanogenesis in vivo using zebrafish.<bold>Key Results: </bold>Kazinol U inhibited the expression and activity of tyrosinase, the rate-limiting enzyme in melanogenesis, and reduced tyrosinase expression and activity in response to cAMP-inducing agents. Kazinol U reduced the expression of other melanogenic enzymes, such as tyrosinase-related protein (Tyrp) 1 and Tyrp2, and down-regulated microphthalmia-associated transcription factor (MITF), the master regulator of the tyrosinase gene family. Moreover, kazinol U induced phosphorylation of AMPK and MAPK proteins, which are MITF inhibitors. It also exhibited anti-melanogenic effects in zebrafish, a recently developed in vivo model.<bold>Conclusions and Implications: </bold>Our findings suggest that kazinol U reduces melanogenesis via its inhibitory effect on MITF and its downstream target genes, tyrosinase, Tyrp1 and Tyrp2. This work may provide a basis for the application of kazinol U for the treatment of hyperpigmentation skin disorders. [ABSTRACT FROM AUTHOR]
- Subjects :
- FLAVANS
BROUSSONETIA
CYTOPROTECTION
CYTOKINES
CELL death
MITOGEN-activated protein kinases
PROTEIN metabolism
PROTEINS
BIOCHEMISTRY
RESEARCH
MELANINS
PHOSPHOTRANSFERASES
ANIMAL experimentation
PHENOMENOLOGICAL biology
RESEARCH methodology
EVALUATION research
COMPARATIVE studies
FISHES
TRANSFERASES
RESEARCH funding
OXIDOREDUCTASES
MELANOGENESIS
CELL lines
EPITHELIAL cells
MICE
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 176
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 134552884
- Full Text :
- https://doi.org/10.1111/bph.14560