Figure 6.

A hypothetical mechanism for the inhibition of eumelanin synthesis by arbutin involving its tyrosinase (TYR) inhibitory and antioxidant activities. Arbutin inhibits the catalytic activity of TYR. It also scavenges reactive oxygen species (ROS) from various sources that can induce melanin synthesis, apoptosis, or tumorigenesis. It can activate the erythroid 2-associated factor 2 (Nrf2)-antioxidant responsive elements (ARE) pathway to enhance the antioxidant capacity of cells. Increased thiol compounds, such as L-cysteine and glutathione, can react with L-DOPAquinon to form DOPA-thiol conjugates, which enter the pheomelanin synthesis pathway. As a result, eumelanin synthesis via DOPAchrome can be selectively downregulated by arbutin. Inhibitory targets of arbutin are indicated with ⊗.