| Abstrakt: |
Objective: Tetrahydrocurcumin (THC) has been used as a component of skin whitening cream. However, very little is known about the mechanisms for how THC regulates melanogenesis. The aim of the present study was to investigate mechanisms involved in the regulation of melanogenesis by THC using B16F10 murine melanoma cells. Methods: B16F10 cells were treated with various concentrations of THC (0–30 µg/mL) in the presence of 0.1 nM ±-melanocyte stimulating hormone (±-MSH). Total melanin content; intracellular tyrosinase activity; and levels of melanogenic proteins, i.e., microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 (TYRP1), and signaling proteins, i.e, Akt, glycogen synthase kinase 3ß (GSK3ß), and ß-catenin, were analyzed. Change in cell morphology was also observed. Results: THC-Treatment caused a significant and dose-dependent decrease in total melanin content compared to control cells treated with a-MSH alone. At the early stage of melanogenesis, when melanin secretion was minimal, THC-treatment caused decreases in the activity of tyrosinase and the levels of tyrosinase and MITF proteins. Conversely, at the late stage of melanogenesis, when melanin secretion was evidently exhibited in control cells, remarkable increases in the intracellular levels of tyrosinase and TYRP1, the melanosomal proteins, were observed in THC-treated cells. THC-treatment caused decreases in Akt and GSK3ß phosphorylation and ß-catenin content. A significant alteration of cell morphology, i.e.elongation and loss of dendritic structure, was also observed. Conclusion: The present study demonstrated that THC-treatment inhibited a-MSH-induced melanin synthesis in B16F10 cells by downregulating MITF and tyrosinase proteins and decreasing tyrosinase activity. In addition, THC inhibited secretion of melanosomes, which appears to be associated with cell morphology alteration accompanying a loss of dendritic structure. THC caused decreases in the phosphorylation of Akt and GSK3ß and the content of ß-catenin, suggesting involvement of GSK3ß activation and subsequent attenuation of ß-catenin signaling in the anti-melanogenic effects of THC. |
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