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The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression
Published on: August 3, 2011
Neobavaisoflavone Inhibits Melanogenesis through the Regulation of Akt/GSK-3β and MEK/ERK Pathways in B16F10 Cells
Da Eun Kim1, Bo Yoon Chang1, Sang Ok Ham2
1Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea.
Abstract:
Previous studies have confirmed the anti-melanogenic effect of the aerial part of Pueraria lobata, however, due to its inherent color, P. lobata has limited commercial use. In this study, an extract (GALM-DC) of the aerial part of P. lobata having improved color by the use of activated carbon was obtained. Furthermore, the active compound neobavaisoflavone (NBI) was identified from GALM-DC. The effect of NBI on melanogenesis, tyrosinase activity, α-glucosidase activity, and mechanism of action in melanocytes was investigated. Tyrosinase activity, melanin contents and the expression of melanin-related genes and proteins were determined in B16F10 cells. NBI reduced melanin synthesis and tyrosinase activity. Furthermore, NBI treatment reduced the mRNA and protein expression levels of MITF, TRP-1, and tyrosinase. NBI also works by phosphorylating and activating proteins that inhibit melanogenesis, such as GSK3β and ERK. Specific inhibitors of Akt/GSK-3β (LY294002) and MEK/ERK (PD98059) signaling prevented the inhibition of melanogenesis by NBI. NBI inhibited melanin production through the regulation of MEK/ERK and Akt/GSK-3β signaling pathways in α-MSH-stimulated B16F10 cells. NBI suppresses tyrosinase activity and melanogenesis through inhibition of α-glucosidase activity. Besides, NBI significantly reduced melanogenesis in a reconstructed human 3D skin model. In conclusion, these results suggest that NBI has potential as a skin-whitening agent for hyperpigmentation.
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