Aglycone of Rh4 Inhibits Melanin Synthesis in B16 Melanoma Cells: Possible Involvement of the Protein Kinase A Pathway

To our knowledge, there is no report that directly shows an inhibitory effect of ginsenoside on melanin synthesis in B16 melanoma cells. Hence, we investigated whether the aglycone of Rh4 (A-Rh4) inhibits melanin synthesis in B16 melanoma cells, and determined the mechanism of melanin inhibition. We isolated 12 ginsenoside compounds from leaves of Panax ginseng and tested them in B16 melanoma cells. It significantly reduced melanin content and tyrosinase activity under alpha-melanocyte stimulating hormone- and forskolin-stimulated conditions. It significantly reduced the cyclic AMP (cAMP) level in B16 melanoma cells, and this might be responsible for the regulation down of MITF and tyrosinase. Phosphorylation of a downstream molecule, a cAMP response-element binding protein, was significantly decreased according to Western blotting and immunofluorescence assay. These data suggest that A-Rh4 has an anti-melanogenic effect via the protein kinase A pathway.