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 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.
Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Pyeong-dong, Jongno-gu, Seoul 110-746, Korea. heunjoolee111@gmail.com.
Heun Joo
HJ
Lee
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong Songpa-gu, Seoul 138-736, Korea. uucm79@hanmail.net.
Woo Jin
WJ
Lee
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong Songpa-gu, Seoul 138-736, Korea. csesnumd@gmail.com.
Sung Eun
SE
Chang
Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Pyeong-dong, Jongno-gu, Seoul 110-746, Korea. gylee0716@hanmail.net.
Ga-Young
GY
Lee
D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects
D000975:Antioxidants; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D006569:Hesperidin; D014442:Monophenol Monooxygenase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
anti-melanogenesis; antioxidant; extracellular signal-regulated kinase 1/2 (Erk1/2); hesperidin; microphthalmia-associated transcription factor (MITF)