Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo.

The rhizoma of , a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of , we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of , and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid () and -4-pentylcyclohex-3-ene-1,2-diol () were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound and (3,3a)-neocnidilide () exhibited antimelanogenesis activities with IC values of 78.9 and 31.1 μM, respectively, without obvious cytotoxicity. Further investigation showed that compound demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 μM) compared to arbutin (20 μM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3,3)-neocnidilide () is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.