saucerneol-d and Hyperpigmentation

Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC(50) values of 188-297 nM in B16 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or other cAMP elevators. Moreover, saucerneol D down-regulated α-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, saucerneol D inhibited α-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.

Topics: alpha-MSH; Cell Survival; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Down-Regulation; Drug Evaluation, Preclinical; Gene Expression; Hormones; Humans; Hyperpigmentation; Lignans; Luciferases; Melanins; Melanocytes; Melanoma; Melanoma, Experimental; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phosphorylation; Saururaceae