Anti-melanogenesis effect of dehydroglyasperin C through the downregulation of MITF via the reduction of intracellular cAMP and acceleration of ERK activation in B16F1 melanoma cells

• Published in: Pharmacological reports 2018-10, Vol.70 (5), p.930-935
• Main Authors: Lim, Ji Won, Ha, Ji Hoon, Jeong, Yoon Ju, Park, Soo Nam
• Format: Article
• Language: English
• Subjects: alpha-MSH - antagonists & inhibitors; alpha-MSH - pharmacology; Animals; Benzopyrans - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Cyclic AMP - metabolism; cyclicAMP; Dehydroglyasperin C; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Drug Safety and Pharmacovigilance; Enzyme Activation - drug effects; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Melanins - biosynthesis; Melanogenesis; Melanoma, Experimental - drug therapy; Melanoma, Experimental - enzymology; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Membrane Glycoproteins - metabolism; Mice; Microphthalmia-Associated Transcription Factor - metabolism; MITF; Monophenol Monooxygenase - metabolism; Original Article; Oxidoreductases - metabolism; Pharmacotherapy; Pharmacy
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2018.02.024

•Dehydroglyasperin C suppressed the protein expression levels of tyrosinase and TRP-1.•Dehydroglyasperin C decreased intracellular tyrosinase activity.•Dehydroglyasperin C downregulated MITF level trough cAMP-CREB pathway.•Dehydroglyasperin C degraded MITF trough the phosphorylation of ERK. In mammals, UV radiation induces melanin synthesis in melanocyte for protecting their skin through the stimulation of α-melanocyte stimulating hormone (α-MSH) from keratinocytes. In this study, the inhibitory effects of dehydroglyasperin C (DGC), an useful component of Glycyrrhiza uralensis (G. uralensis), was investigated on melanogenesis induced by α-melanocyte stimulating hormone (α-MSH) and its mechanisms. Melanogenesis suppression effect of DGC on α-MSH induced B16F1 melanoma cells. The cell viability was measured by MTT assay. Expression and phosphorylation of melanogeic protein were conducted using western blot. cAMP acceleration was measured by cAMP immunoassay kit. To investigate whitening mechanism, we used ERK inhibitor (PD98059). DGC decreased intra cellular tyrosinase (TYR) activity and expression of melanin synthesis related proteins (TYR and TRP-1) in a dose-dependent manner on α-MSH induced melanogenesis. In addition, DGC induced the downregulation of MITF (melanocyte-specific transcription factor) through suppression of cAMP-CREB pathway. Also, phosphorylation of extracellular signal regulated kinase (ERK) decreased MITF by DGC treatment. Therefore, DGC could be used as a whitening ingredient in skin and clinical usage against hyperpigmentation.