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

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 determi...

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Bibliographic Details
Published in:International journal of molecular sciences 2015-08, Vol.16 (8), p.18384-18395
Main Authors: Lee, Heun Joo, Lee, Woo Jin, Chang, Sung Eun, Lee, Ga-Young
Format: Article
Language:English
Subjects:
anti-melanogenesis
antioxidant
Antioxidants
Antioxidants - pharmacology
Cell Line, Tumor
extracellular signal-regulated kinase 1/2 (Erk1/2)
hesperidin
Hesperidin - pharmacology
Humans
Kinases
Melanins - metabolism
Melanocytes - drug effects
Melanocytes - metabolism
Melanocytes - pathology
microphthalmia-associated transcription factor (MITF)
Microphthalmia-Associated Transcription Factor - metabolism
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Monophenol Monooxygenase - metabolism
Proteolysis - drug effects
Skin diseases
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms160818384