TY - JOUR
T1 - 7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor
AU - Kim, Ji Hye
AU - Lee, Jae Eun
AU - Kim, Taewon
AU - Yeom, Myung Hun
AU - Park, Jun Seong
AU - di Luccio, Eric
AU - Chen, Hanyong
AU - Dong, Zigang
AU - Lee, Ki Won
AU - Kang, Nam Joo
N1 - 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.
PY - 2020/12/3
Y1 - 2020/12/3
N2 - 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.
AB - 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.
KW - 3′
KW - 4′-Trihydroxyisoflavone
KW - 7
KW - depigmentation
KW - melanocortin 1 receptor
KW - melanogenesis
KW - α-MSH
UR - http://www.scopus.com/inward/record.url?scp=85097831661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097831661&partnerID=8YFLogxK
U2 - 10.3389/fmolb.2020.577284
DO - 10.3389/fmolb.2020.577284
M3 - Article
C2 - 33344501
AN - SCOPUS:85097831661
SN - 2296-889X
VL - 7
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
M1 - 577284
ER -