Inhibitory effects of 4-n-butylresorcinol on tyrosinase activity and melanin synthesis.
In this study, we investigated the effects of 4-n-butylresorcinol on melanogenesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that 4-n-butylresorcinol significantly inhibits melanin synthesis in a concentration-dependent manner. In addition, it was also found to inhibit the activity of tyrosinase, the rate-limiting melanogenic enzyme. Several reports have indicated that the activation of extracellular signal-regulated kinase (ERK) or of Akt reduces melanin synthesis via microphthalmia-associated transcription factor (MITF) down-regulation. Accordingly, we examined the effects of 4-n-butylresorcinol on the ERK and Akt signaling pathways. 4-n-Butylresorcinol did not induce ERK, Akt activation, or MITF degradation, and had no effect on cAMP response element binding protein (CREB) phosphorylation, which stimulates MITF expression. In contrast, 4-n-butylresorcinol strongly reduced tyrosinase activity in a cell-free system. Moreover, 4-n-butylresorcinol showed an additive effect in combination with hinokitiol, which reduces MITF expression. These results show that the hypopigmentary effect of 4-n-butylresorcinol results from its direct inhibition of tyrosinase.
Kim
Dong-Seok
DS
Department of Dermatology, Seoul National University College of Medicine, Chongno-Gu, Korea.
Kim
So-Young
SY
Park
Seo-Hyoung
SH
Choi
Yeong-Gon
YG
Kwon
Sun-Bang
SB
Kim
Myo-Kyoung
MK
Na
Jung-Im
JI
Youn
Sang-Woong
SW
Park
Kyoung-Chan
KC
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D017496:Hypopigmentation / Q000139:chemically induced / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012880:Skin Pigmentation; D014334:Tropolone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
C508220:4-n-butylresorcinol; D004338:Drug Combinations; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D039821:Monoterpenes; D012118:Resorcinols; D014334:Tropolone; D014442:Monophenol Monooxygenase; C009479:beta-thujaplicin