Hypopigmentary effects of 4-n-butylresorcinol and resveratrol in combination.

In the present study, the effects of 4-n-butylresorcinol and/or resveratrol on melanogenesis were studied. To achieve synergistic effects and avoid potential adverse effects, combinations of the agents in low concentrations were investigated. Our results show that 1 microM of 4-n-butylresorcinol and 1 microM of resveratrol did not individually inhibit melanin synthesis. However, the combination of 4-n-butylresorcinol (1 microM) and resveratrol (1 microM) significantly reduced melanin synthesis. Furthermore, 4-n-butylresorcinol (10 microM) and resveratrol (10 microM) decreased melanogenesis much stronger. 4-n-Butylresorcinol is reported to directly inhibit tyrosinase, the rate-limiting melanogenic enzyme, without changing tyrosinase levels. Our results also showed that resveratrol did not directly inhibit tyrosinase at 0.1-10 microM. Literature has reported that resveratrol led to post-transcriptional regulation of tyrosinase. However, Western blot analysis showed that neither 4-n-butylresorcinol nor resveratrol alone decreased tyrosinase protein levels. Surprisingly, the combination of 4-n-butylresorcinol and resveratrol reduced tyrosinase levels. Therefore, these results indicate that the synergistic hypopigmentary effect of 4-n-butylresorcinol and resveratrol results from a decreased level of tyrosinase possibly resulting from synergistic action of 4-n-butylresorcinol on tyrosinase alteration by resveratrol.