Anti-melanogenic Activity of Demethoxycurcumin via Microphthalmia-associated Transcription Factor (MITF) in Melanocyte

Abstract

Natural products from plants, fungi, bacteria and other organisms continue to be used in pharmaceutical preparations. The anti-melanogenic activity of demethoxycurcumin (DC), a compound of C. aromatica, and its molecular mechanism was investigated in mouse melan-a cells. DC significantly inhibited melanin synthesis and down-regulated the expression of the microphthalmia-associated transcription factor (MITF) which suppresses the expression of tyrosinase, tyrosinase-related protein-1, and -2 (TRP-1, -2). Further analysis revealed that DC suppressed the SRY-related HMG-box 10 (SOX10), critical transcription factors of MITF. DC also effectively inhibited DNA-binding activity of phosphor-cAMP response element binding protein (p-CREB), an up-stream regulatory factor of MITF. DC exhibit the up-regulation of ERK and AKT activation through mitogen-activated protein kinases (MAP kinase) pathway but there is no effect of phosphorylation of MITF because MITF is already decreased by SOX10 and p-CREB-DNA binding. These findings suggest that DC might serve as a candidate for an effective melanogenic inhibitor in melanocytes via the regulation of MITF signaling pathway. The anti-inflammatory activity of pinosylvin (PS), a natural stilbenoid from the heartwood of Pinaceae, was investigated in human keratinocytes, HaCaT cells. PS inhibited the UV-induced production of prostaglandin E2 (PGE2) in HaCaT cells. The suppression of PGE2 productions by PS was correlated with the down-regulation of mRNA and protein expression of cyclooxygenase-2 (COX-2). Further analysis revealed that PS suppressed the activation of MAP kinases, JNK, c-FOS and c-JUN signaling. These findings suggest that PS might serve as a candidate for a potential UV-induced anti-inflammaging agent via the regulation of MAP kinase signaling pathway.