Inhibitory Effect and Molecular Mechanism of an Anti-tyrosinase in B16F1 Melanoma Cells by α-mangostin, Isolated from Mangosteen Pericarp

Tyrosinase is the key enzyme of melanogenesis which is responsible for hyperpigmentation and food browning. Thus, investigations on natural and safe tyrosinase inhibitors has received massive attention around the globe. Phytochemistry work on Garcinia mangostana L. or locally known as mangosteen using various chromatography techniques led to the isolation of the chief constituent, α-mangostin which showed outstanding anti tyrosinase activity. The compound remarkably showed better inhibition on melanogenesis induced by α-MSH compare to positive control used, arbutin and kojic acid when tested on B16F1 melanoma cell line. The inhibition of intracellular tyrosinase activity was found to be exerted at the protein expression level when analyzed by immunoblot and tyrosinase zymography. The expression level of microphthalmia-associated transcription factor (MITF) was reduced by treatment of α-mangostin. The down-regulation of intracellular tyrosinase expression seemed to correlate with decrease in MITF protein level which is the key factor for the genes involved in melanogenesis. ABTS assay on α-mangostin indicated that the compound possessed moderate antioxidant activity with IC50 value of 28.8.µg/ml. The overall results suggest that α-mangostin has strong and potent anti-melanogenic activity that is exerted by direct inhibition of tyrosinase enzyme activity and by down-regulation of the genes expression involved in the melanogenesis pathways.