Verbenone, a major compound of rosemary hydrosol inhibits melanogenesis and oxidative stress in B16F10 mouse melanoma cell

Abstract

In the present study, we investigated the effect of verbenone, an active compound present in Rosmarinus officinalis L. hydrosol extract, on melanin synthesis and the molecular mechanism of melanogenesis in B16F10 mouse melanoma cells. The cellular melanin content and tyrosinase activity of the 2.5 mM verbenone-treated cells were significantly reduced below the levels of the kojic acid- treated cells, consistent with suppression of melanin biosynthesis by verbenone via inhibition of tyrosinase activity.Also verbenone inhibits the expression of melanogenesis-related proteins including MITF(Microphthalmia-associated transcription factor), tyrosinase and tyrosinase-related protein (TRP)s in α-MSH(a-melanocyte-stimulating hormone)-stimulated B16F10 cells. Moreover, the phospho-Akt was significantly enhanced but phospho-p38 MAPK was reduced and no effect phospho-ERK. Furthermore, the ROS generation submitted to an oxidative stress by H2O2treatment was completely inhibited by pre-treatment of verbenone,which is consistent with the increase in mRNA level of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in B16F10 cells. These data suggest that verbenone inhibits melanogenesis signaling by both inhibiting theexpression of melanogenesis protein and activating the Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRP-1 and TRP-2. Therefore, verbenone would be a useful therapeutic agent for treating hyperpigmentation and can be applicable for cosmetics as skin-whitening agents.