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

Jin Hee Kim, Seung Hwa Baek, Dong Hyun Kim, Tae Young Choi, Tae Jin Yoon, Jae Sung Hwang, Mee Ree Kim, Ho Jeong Kwon, Choong Hwan Lee

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

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 IC50 (half-maximal inhibitory concentration) value of 5.0 μM 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.

Original languageEnglish
Pages (from-to)1227-1235
Number of pages9
JournalJournal of Investigative Dermatology
Volume128
Issue number5
DOIs
Publication statusPublished - 2008 May

Bibliographical note

Funding Information:
This research was supported by a grant (PDM1600526) from Plant Diversity Research Center of the 21st Century Frontier Research Program, which is funded by the Ministry of Science and Technology of the Korean Government and supported by a grant (code no. 2007030134039) from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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