Three new butanolides, isophilippinolide A, philippinolide A, and philippinolide B, an amide, cinnaretamine were isolated from the roots of Cinnamomum philippinense to be identified using spectroscopic analysis. Four isolated compounds were screened for free radical scavenging ability, metal chelating power assay and ferric reducing antioxidant power assay (FRAP). Cinnaretamine showed the powerful anti-oxidative properties in 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, as well as a reducing activity; and all compounds presented minor inhibition of metal chelating capacities. The anti-tyrosinase effects of C. philippinense constitutes were calculated the inhibition of hydroxylation of L-tyrosine to L-dopa according to an in vitro mushroom tyrosinase assay, and all testing samples illustrated slight mushroom tyrosinase inhibitory belongings. Isophilippinolide A exhibited inhibitory effectivenesses against A375.S2 melanoma cell line in the cell viability assay at concentration rages from 0 to 200 M at 24 h treatment. Propidium iodide staining and flow cytometry analyses were applied to assess cell cycle accumulative distribution, and found that isophilippinolide A caused sub-G1 phase accumulation in a dose-dependent manner for apoptosis to inhibit cell growth. Further investigation revealed that isophilippinolide A-induced A375.S2 cells with the increasing of caspase-dependent apoptotic proteins to trigger related pathway mechanisms according to the western blotting results. Finally, isophilippinolide A just displayed small cytotoxicities to human normal epidermal cells (melanocytes) and dermal cells (fibroblasts). Taken together, these results suggested that C. philippinense compounds could be considered as functional ingredients in cosmetics, food or pharmaceutical products, especially on the anticancer ability indicating the promising chemopreventive agents to human skin melanoma cells.
Journal of Agricultural and Food Chemistry 62(5),1057-1065