PUBLICATION
Downregulation of Melanin Synthesis by Haginin A and Its Application to In Vivo Lightening Model
- Authors
- Kim, J.H., Baek, S.H., Kim, D.H., Choi, T.Y., Yoon, T.J., Hwang, J.S., Kim, M.R., Kwon, H.J., and Lee, C.H.
- ID
- ZDB-PUB-071129-5
- Date
- 2008
- Source
- The Journal of investigative dermatology 128(5): 1227-1235 (Journal)
- Registered Authors
- Choi, Tae-Young
- Keywords
- none
- MeSH Terms
-
- Agaricales/enzymology
- Animals
- Cells, Cultured
- Chromones/pharmacology
- Down-Regulation/drug effects
- Down-Regulation/physiology
- Enzyme Inhibitors/pharmacology
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Flavonoids/pharmacology
- Guinea Pigs
- Isoflavones/chemistry
- Isoflavones/pharmacology*
- Lespedeza*
- MAP Kinase Signaling System/drug effects
- Melanins/biosynthesis*
- Melanocytes/cytology
- Melanocytes/drug effects*
- Melanocytes/metabolism*
- Mice
- Mice, Inbred C57BL
- Microphthalmia-Associated Transcription Factor/metabolism
- Models, Animal
- Monophenol Monooxygenase/antagonists & inhibitors
- Monophenol Monooxygenase/metabolism
- Morpholines/pharmacology
- Phosphorylation/drug effects
- Plant Extracts/chemistry
- Plant Extracts/pharmacology*
- Proto-Oncogene Proteins c-akt/metabolism
- Skin Pigmentation/drug effects
- Streptomyces/drug effects
- Streptomyces/metabolism
- Ultraviolet Rays
- Zebrafish
- PubMed
- 18037902 Full text @ J. Invest. Dermatol.
Citation
Kim, J.H., Baek, S.H., Kim, D.H., Choi, T.Y., Yoon, T.J., Hwang, J.S., Kim, M.R., Kwon, H.J., and Lee, C.H. (2008) Downregulation of Melanin Synthesis by Haginin A and Its Application to In Vivo Lightening Model. The Journal of investigative dermatology. 128(5):1227-1235.
Abstract
Haginin A, an isoflav-3-ens isolated from the branch of Lespedeza cyrtobotrya, is almost unknown. Here, we report that haginin A exhibits a strong hypopigmentary effect in Melan-a cells and significantly inhibits melanin synthesis. Haginin A shows potent inhibitory effects with an IC(50) (half-maximal inhibitory concentration) value of 5.0 muM on mushroom tyrosinase activity, and functioned as a noncompetitive inhibitor. Also, haginin A decreased microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1) protein production. To identify the signaling pathway of haginin A, the ability of haginin A to influence extracellular signal-regulated protein kinase (ERK) and Akt/protein kinase B (PKB) activation was investigated. Apparently, haginin A induced ERK and Akt/PKB in a dose-dependent manner. In addition, the specific inhibition of the ERK and the Akt/PKB signaling pathways by PD98059 and LY294002, respectively, increased melanin synthesis. Furthermore, haginin A decreased UV-induced skin pigmentation in brown guinea-pigs. Also, haginin A presented remarkable inhibition on the body pigmentation in the zebrafish model system and decreased tyrosinase activity. Together, haginin A is an effective inhibitor of hyperpigmentation caused by UV irradiation or by pigmented skin disorders through downregulation via ERK and Akt/PKB activation, MITF, and also by the subsequent downregulation of tyrosinase and TRP-1 production.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping