Downregulation of melanin synthesis by haginin A and its application to in vivo lightening model.

Research paper by 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

Indexed on: 27 Nov '07Published on: 27 Nov '07Published in: Journal of Investigative Dermatology


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.