Three new butanolides,
isophilippinolide A, philippinolide A, and philippinolide B, and an
amide, cinnaretamine, were isolated from the roots of Cinnamomum philippinense to be identified by spectroscopic analysis. Four isolated compounds were screened to examine their radical-scavenging ability,
metal-chelating power, and ferric-reducing
antioxidant power assay (FRAP). Cinnaretamine showed powerful antioxidative properties in the
1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and a reducing activity; all compounds presented minor inhibition of
metal-chelating capacities. The effects of anti-
tyrosinase of C. philippinense constituents were determined by the level of the suppression of hydroxylation that turned from
L-tyrosine to
L-dopa through an in vitro mushroom
tyrosinase assay, and all testing samples illustrated slight mushroom
tyrosinase inhibitory properties.
Isophilippinolide A exhibited inhibitory effectivenesses against the A375.S2
melanoma cell line in a cell viability assay at concentrations ranging from 0 to 200 μM for 24 h.
Propidium iodide staining and flow cytometry analyses were applied to assess cell cycle accumulative distribution. It was discovered that
isophilippinolide A caused sub-G1 phase accumulation in positive correlation for apoptosis to inhibit cell growth. Further investigation revealed that
isophilippinolide A induced A375.S2 cells with an increase of
caspase-dependent apoptotic
proteins to trigger correlated pathway mechanisms according to Western blotting results. Finally,
isophilippinolide A displayed only low cytotoxicities to human normal epidermal cells (melanocytes) and dermal cells (fibroblasts). Altogether, the results implied C. philippinense compounds could be considered functional ingredients in
cosmetics, foods, and
pharmaceutical products, particularly for their anticancer ability on human skin
melanoma cells.