Agents to control melanogenesis are in demand for the development of
cosmetics to improve
pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of
flavonoids on melanogenesis in the melanogenic cells model, murine B16F10
melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 μM of the 4'-O-methylated
flavonoids,
diosmetin (4'-O-methylluteolin),
acacetin (4'-O-methylapigenin) or
kaempferide (4'-O-methylkaempferol), increased the
melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 μM
acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4'-OH-type
flavonoids,
luteolin,
apigenin and
kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic
proteins, we found that the cells treated with 4'-O-methylated
flavonoids showed higher
tyrosinase activity, as well as upregulation of
tyrosinase expression, preceded by activation of
cAMP response element binding protein (CREB) and
extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4'-O-methyl group of
flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10
melanoma cells.