Figure 6.

Proposed molecular mechanism of zerumbone (ZER) for attenuation of α-MSH-induced melanogenesis. Black T bar indicates suppression and black arrows indicate activation signaling. α-MSH stimulates MITF mRNA expression through PKA-CREB axis-mediated transcription. Increased ERK1/2 phosphorylation by ZER suppresses MITF. Suppression of MITF by ZER-mediated ERK1/2 phosphorylation down-regulates transcription of genes, such as tyrosinase, TYRP1, and TYRP2, encoding melanogenic enzymes and results in inhibition of melanogenesis. α-MSH: alpha-melanocyte stimulating hormone; MC1R: melanocortin 1 receptor; PKA: protein kinase A; CREB: cAMP response element binding protein; MITF: micropthalmia-associated transcription factor; TYRP1: tyrosinase-related protein 1; TYRP2: tyrosinase-related protein 2; MEK1/2: mitogen-activated protein kinase kinases; and, ERK1/2: extracellular signal-regulated kinases.