Anti-Melanogenic Effect of Dendropanax morbiferus and Its Active Components via Protein Kinase A/Cyclic Adenosine Monophosphate-Responsive Binding Protein- and p38 Mitogen-Activated Protein Kinase-Mediated Microphthalmia−Associated Transcription Factor Downregulation

Abstract

<i>Dendropanax morbiferus</i> H. Lév has been reported to have some pharmacologic activities and also interested in functional cosmetics. We found that the water extract of <i>D. morbiferus</i> leaves significantly inhibited tyrosinase activity and melanin formation in α-melanocyte stimulating hormone (MSH)-induced B16-F10 cells. <i>D. morbiferus</i> reduced melanogenesis-related protein levels, such as microphthalmia-associated transcription factor (MITF), TRP-1, and TRP-2, without any cytotoxicity. Two active ingredients of <i>D. morbiferus,</i> (10E)-9,16-dihydroxyoctadeca-10,17-dien-12,14-diynoate (DMW-1) and (10E)-(-)-10,17-octadecadiene-12,14-diyne-1,9,16-triol (DMW-2) were identified by testing the anti-melanogenic effects and then by liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis. DMW-1 and DMW-2 significantly inhibited melanogenesis by the suppression of protein kinase A (PKA)/cyclic AMP (cAMP)-responsive binding protein (CREB) and p38 MAPK phosphorylation. DMW-1 showed a better inhibitory effect than DMW-2 in α-MSH-induced B16-F10 cells. <i>D. morbiferus</i> and its active component DMW-1 inhibited melanogenesis through the downregulation of cAMP, p-PKA/CREB, p-p38, MITF, TRP-1, TRP-2, and tyrosinase. These results indicate that <i>D. morbiferus</i> and DMW-1 may be useful ingredients for cosmetics and therapeutic agents for skin hyperpigmentation disorders.