title: (-)-Epigallocatechin-3-gallate and hinokitiol reduce melanin synthesis via decreased MITF production.
abstract: In this study, the effects of (-)-epigallocatechin-3-gallate (EGCG) and/or hinokitiol (beta-thujaplicin) on melanogenesis were investigated. Our results showed that both EGCG and hinokitiol significantly inhibited melanin synthesis in a concentration-dependent manner, and that their hypopigmenting effects were stronger than that of kojic acid, which is known to inhibit melanin formation in melanocytes and melanoma cells. Interestingly, EGCG did not show any additive hypopigmenting effect in combination with kojic acid, though EGCG did show a synergistic effect in combination with hinokitiol. Several reports indicate that the activation of extracellular signal-regulated kinase (ERK) induces microphthalmia-associated transcription factor (MITF) degradation. Accordingly, the effects of EGCG and hinokitiol on the ERK signaling pathway were examined. EGCG and hinokitiol induced neither ERK activation nor MITF degradation. On the other hand, both EGCG and hinokitiol reduced the protein levels of MITF and of tyrosinase, the rate limiting melanogenic enzyme, whereas kojic acid had no effect. In addition, hinokitiol strongly downregulated the activity of tyrosinase, whereas EGCG or kojic acid had only a little effect. These results show that both EGCG and hinokitiol reduce MITF production, and suggest that reduced tyrosinase activity by hinokitiol explains their synergistic effect on melanogenesis.
authors.affiliation: Research Division for Human Life Sciences, Seoul National University, Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Seo-Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Sun-Bang
authors.initials: SB
authors.lastname: Kwon
authors.forename: Kapsok
authors.initials: K
authors.lastname: Li
authors.forename: Sang-Woong
authors.initials: SW
authors.lastname: Youn
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D039821:Monoterpenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D004338:Drug Combinations; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D039821:Monoterpenes; D014157:Transcription Factors; D014334:Tropolone; D002392:Catechin; C045651:epigallocatechin gallate; C009479:beta-thujaplicin