Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders.

Effect of Phlorotannins Isolated From Eisenia bicyclis on Melanogenesis in Mouse B16 Melanoma Cells

Phlorotannins isolated from brown algae, such as Eisena bicyclis, have positive physiological effects, including anti-cancer, anti-inflammatory, and anti-Alzheimer’s disease. Although phlorotannins have been shown to inhibit tyrosinase, an enzyme essential for melanogenesis, their effect on melanogenesis remains unexplored. Thus, we isolated phlorotannins from E. bicyclis and examined their effects on α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in murine B16 melanoma cells. Both fucofuroeckol-A (FF-A) and phlorofucofuroeckol-A (PFF-A) suppressed α-MSH-induced melanogenesis. Neither inhibited human tyrosinase (TYR) activity, but both inhibited tyrosinase-related protein-2 activity. FF-A downregulated the expression of microphthalmia-associated transcription factor and TYR, which subsequently suppressed melanin production. These results suggest that phlorotannins could be beneficial as melanin control drugs for hyperpigmentation disorders.

Tyrosinase activity and melanogenic effects of Lespedeza bicolor extract in vitro and in vivo

Lespedeza bicolor (L. bicolor) is used for medicinal purposes because of its various biological and pharmacological activities. In this study, the effects of L. bicolor ethanol extract on the treatment of vitiligo were investigated. The determination of melanin content in melanocytes was measured using B16 melanoma cells and C57BL/6J Ler-vit/vit mice. Finally, the quercetin content in L. bicolor were qualitatively analyzed using HPLC. The results obviously indicated that the L. bicolor extract enhanced melanogenesis and increased tyrosinase activity in cultured melanoma cells and C57BL/6J Ler-vit/vit mice. Treatment with L. bicolor extract led to a higher content of melanin and eumelanin in C57BL/6J Ler-vit/vit mice hair than in control (untreated) mice, which demonstrated the therapeutic effect of hair-graying associated with vitiligo. There was a notable increase in melanocytes in the skin of C57BL/6J Ler-vit/vit mice treated with L. bicolor extract compared with the control. L. bicolor extract was a potent tyrosinase and melanin synthesis activator in B16 melanoma cells. C57BL/6J Ler-vit/vit mice treated with L. bicolor extract had significantly higher melanin content in hair than the untreated control. The results suggest that L. bicolor extract is a potential alternative treatment for improvement of vitiligo.

Anti-proliferative Activity of Some Oleanolic Acid Derivatives with Potent Topoisomerase Inhibitory Activity on B16 Melanoma Cells

Our previous study included the semisynthetic reactions on oleanolic acid, a common wood-derived oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid were synthesized based on docking studies and tested for their topoisomerase I and IIα inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C-13 and C-17. Some of these compounds act as dual inhibitors for both topoisomerase I and IIα giving new anticancer agents. The cytotoxic activity of these compounds on B16 melanoma cancer cells was evaluated. Results showed that most of these compounds have a higher cytotoxic activity on B16 melanoma cells.