Kazinol U inhibits melanogenesis through the inhibition of tyrosinase-related proteins via AMP kinase activationopen access
- Authors
- Lim, Jihyun; Nam, Sorim; Jeong, Ji Hye; Kim, Min Jung; Yang, Young; Lee, Myeong-Sok; Lee, Hee Gu; Ryu, Jae-Ha; Lim, Jong-Seok
- Issue Date
- Mar-2019
- Publisher
- WILEY
- Citation
- BRITISH JOURNAL OF PHARMACOLOGY, v.176, no.5, pp 737 - 750
- Pages
- 14
- Journal Title
- BRITISH JOURNAL OF PHARMACOLOGY
- Volume
- 176
- Number
- 5
- Start Page
- 737
- End Page
- 750
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/3745
- DOI
- 10.1111/bph.14560
- ISSN
- 0007-1188
1476-5381
- Abstract
- Background and Purpose 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.
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