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

H. Lév has been reported to have some pharmacologic activities and also interested in functional cosmetics. We found that the water extract of leaves significantly inhibited tyrosinase activity and melanin formation in α-melanocyte stimulating hormone (MSH)-induced B16-F10 cells. reduced melanogenesis-related protein levels, such as microphthalmia-associated transcription factor (MITF), TRP-1, and TRP-2, without any cytotoxicity. Two active ingredients of (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. 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 and DMW-1 may be useful ingredients for cosmetics and therapeutic agents for skin hyperpigmentation disorders.