Int. J. Mol. Sci. 2013, 14(10), 20443-20458; doi:10.3390/ijms141020443
Article

Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells

1,†email, 2,†email, 3email, 1email, 4email, 5,6email, 5email, 1email and 5,* email
Received: 10 May 2013; in revised form: 19 September 2013 / Accepted: 25 September 2013 / Published: 14 October 2013
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Abstract: Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions.
Keywords: gallic acid; melanogenesis; microphthalmia-associated transcription factor (MITF); tyrosinase; TRP1; Dct; MEK/ERK; PI3K/Akt; Wnt/β-catenin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Su, T.-R.; Lin, J.-J.; Tsai, C.-C.; Huang, T.-K.; Yang, Z.-Y.; Wu, M.-O.; Zheng, Y.-Q.; Su, C.-C.; Wu, Y.-J. Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells. Int. J. Mol. Sci. 2013, 14, 20443-20458.

AMA Style

Su T-R, Lin J-J, Tsai C-C, Huang T-K, Yang Z-Y, Wu M-O, Zheng Y-Q, Su C-C, Wu Y-J. Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells. International Journal of Molecular Sciences. 2013; 14(10):20443-20458.

Chicago/Turabian Style

Su, Tzu-Rong; Lin, Jen-Jie; Tsai, Chi-Chu; Huang, Tsu-Kei; Yang, Zih-Yan; Wu, Ming-O; Zheng, Yu-Qing; Su, Ching-Chyuan; Wu, Yu-Jen. 2013. "Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells." Int. J. Mol. Sci. 14, no. 10: 20443-20458.


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