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Int. J. Mol. Sci. 2015, 16(8), 18384-18395; doi:10.3390/ijms160818384

Hesperidin, A Popular Antioxidant Inhibits Melanogenesis via Erk1/2 Mediated MITF Degradation

1
Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Pyeong-dong, Jongno-gu, Seoul 110-746, Korea
2
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong Songpa-gu, Seoul 138-736, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 13 May 2015 / Revised: 9 July 2015 / Accepted: 29 July 2015 / Published: 7 August 2015
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Abstract

Regulation of melanogenesis has been the focus of treatment for hyperpigmentary skin disorders. Although hesperidin is one of the most well-known, naturally occurring flavonoids with antioxidant and anti-inflammatory effect, its anti-melanogenic effect is not known. The present study aims to determine the anti-melanogenic effect of hespiridin as well as its underlying molecular mechanisms. Melanin contents were measured in normal human melanocytes and B16F10 melanoma cells. Protein and mRNA levels of tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1) and TRP-2 were determined. Melanogenesis-regulating signals were examined. In results, hesperidin strongly inhibited melanin synthesis and tyrosinase activity. Hesperidin decreased tyrosinase, TRP-1, and TRP-2 protein expression but increased phospho-extracellular signal-regulated kinase 1/2 (p-Erk1/2) expression. Specific inhibitor of Erk1/2 or proteasome inhibitor reversed the inhibition of melanogenesis induced by hesperidin. Taken together, hesperidin, a popular antioxidant, stimulated Erk1/2 phosphorylation which subsequently degraded MITF which resulted in suppression of melanogenic enzymes and melanin synthesis. View Full-Text
Keywords: hesperidin; anti-melanogenesis; microphthalmia-associated transcription factor (MITF); extracellular signal-regulated kinase 1/2 (Erk1/2); antioxidant hesperidin; anti-melanogenesis; microphthalmia-associated transcription factor (MITF); extracellular signal-regulated kinase 1/2 (Erk1/2); antioxidant
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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. (CC BY 4.0).

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Lee, H.J.; Lee, W.J.; Chang, S.E.; Lee, G.-Y. Hesperidin, A Popular Antioxidant Inhibits Melanogenesis via Erk1/2 Mediated MITF Degradation. Int. J. Mol. Sci. 2015, 16, 18384-18395.

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