In:
British Journal of Pharmacology, Wiley, Vol. 176, No. 5 ( 2019-03), p. 737-750
Abstract:
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. Experimental Approach 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. Key Results 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. Conclusions and Implications 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.
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2029728-2
SSG:
15,3
