Downregulation of melanin synthesis by haginin A and its application to in vivo lightening model.
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 microM 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.
1Natural Medicines Research Center, KRIBB, Daejeon, Korea.
Jin Hee
JH
Kim
Seung Hwa
SH
Baek
Dong Hyun
DH
Kim
Tae Young
TY
Choi
Tae Jin
TJ
Yoon
Jae Sung
JS
Hwang
Mee Ree
MR
Kim
Ho Jeong
HJ
Kwon
Choong Hwan
CH
Lee
D000363:Agaricales / Q000201:enzymology; D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006168:Guinea Pigs; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D029884:Lespedeza; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D023421:Models, Animal; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism; D014466:Ultraviolet Rays; D015027:Zebrafish
D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007529:Isoflavones; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009025:Morpholines; D010936:Plant Extracts; C528896:haginin A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one