7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor

Ji Hye Kim, Jae Eun Lee, Taewon Kim, Myung Hun Yeom, Jun Seong Park, Eric di Luccio, Hanyong Chen, Zigang Dong, Ki Won Lee, Nam Joo Kang

Research output: Contribution to journalArticlepeer-review

Abstract

7,3′,4′-Trihydroxyisoflavone (7,3′,4′-THIF) is a metabolite of daidzein which is a representative isoflavone found in soybean. Recent studies suggested that 7,3′,4′-THIF exerts a hypopigmentary effect in B16F10 cells, however, its underlying molecular mechanisms and specific target protein remain unknown. Here, we found that 7,3′,4′-THIF, but not daidzein, inhibited α-melanocyte-stimulating hormone (MSH)-induced intracellular and extracellular melanin production in B16F10 cells by directly targeting melanocortin 1 receptor (MC1R). Western blot data showed that 7,3′,4′-THIF inhibited α-MSH-induced tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) expressions through the inhibition of Microphthalmia-associated transcription factor (MITF) expression and cAMP response element-binding (CREB) phosphorylation. 7,3′,4′-THIF also inhibited α-MSH-induced dephosphorylation of AKT and phosphorylation of p38 and cAMP-dependent protein kinase (PKA). cAMP and Pull-down assays indicated that 7,3′,4′-THIF strongly inhibited forskolin-induced intracellular cAMP production and bound MC1R directly by competing with α-MSH. Moreover, 7,3′,4′-THIF inhibited α-MSH-induced intracellular melanin production in human epidermal melanocytes (HEMs). Collectively, these results demonstrate that 7,3′,4′-THIF targets MC1R, resulting in the suppression of melanin production, suggesting a protective role for 7,3′,4′-THIF against melanogenesis.

Original languageEnglish (US)
Article number577284
JournalFrontiers in Molecular Biosciences
Volume7
DOIs
StatePublished - Dec 3 2020

Bibliographical note

Funding Information:
Funding. This research was financially supported by the Bio & Medical Technology Development Program (2018M3A9H3025030), National Research Foundation funded by the Ministry of Science and ICT, South Korea.

Publisher Copyright:
© Copyright © 2020 Kim, Lee, Kim, Yeom, Park, di Luccio, Chen, Dong, Lee and Kang.

Keywords

  • 3′
  • 4′-Trihydroxyisoflavone
  • 7
  • depigmentation
  • melanocortin 1 receptor
  • melanogenesis
  • α-MSH

PubMed: MeSH publication types

  • Journal Article

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