Inhibitory effects of 4-n-butylresorcinol on tyrosinase activity and melanin synthesis

Biol Pharm Bull. 2005 Dec;28(12):2216-9. doi: 10.1248/bpb.28.2216.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Combinations
  • Drug Synergism
  • Humans
  • Hypopigmentation / chemically induced
  • Hypopigmentation / metabolism
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis*
  • Melanins / chemistry
  • Mice
  • Microphthalmia-Associated Transcription Factor / antagonists & inhibitors
  • Microphthalmia-Associated Transcription Factor / chemistry
  • Microphthalmia-Associated Transcription Factor / drug effects
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / drug effects
  • Monophenol Monooxygenase / metabolism
  • Monoterpenes / chemistry
  • Monoterpenes / pharmacology
  • Resorcinols / chemistry
  • Resorcinols / pharmacology*
  • Signal Transduction / drug effects
  • Skin Pigmentation
  • Tropolone / analogs & derivatives
  • Tropolone / chemistry
  • Tropolone / pharmacology


  • 4-n-butylresorcinol
  • Drug Combinations
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Monoterpenes
  • Resorcinols
  • Tropolone
  • Monophenol Monooxygenase
  • beta-thujaplicin