Article date: March 2019
By: Jihyun Lim, Sorim Nam, Ji Hye Jeong, Min Jung Kim, Young Yang, Myeong‐Sok Lee, Hee Gu Lee, Jae‐Ha Ryu, Jong‐Seok Lim in Volume 176, Issue 5, pages 737-750
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.
DOI: 10.1111/bph.14560
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