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.