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Anticancer Res. 1999 Sep-Oct;19(5A):3769-74.

The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis.

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Department of Dermatology, Kobe University School of Medicine, Japan.


Oral vitamin E (alpha-tocopherol) supplementation has been reported to improve facial hyperpigmentation. The compound of alpha-tocopherol and ferulic acid, also an antioxidant connected with an ester bond, alpha-tocopheryl ferulate (alpha-TF) can absorb ultraviolet (UV) radiation and thus maintain tocopherol in a stable state. Our aim was to determine whether alpha-TF can be applied to improve and prevent facial hyperpigmentation induced by UV as a whitening agent as well as an antioxidant. In this study, the effects of alpha-TF on melanogenesis were examined using cultured human melanoma cells and normal human melanocytes in vitro. alpha-TF solubilized in 0.5% lecithin inhibited melanization significantly at the concentration of 30 micrograms/ml compared with arbutin (100 micrograms/ml), kojic acid (100 micrograms/ml), ascorbic acid (600 micrograms/ml), and tranexamic acid (600 micrograms/ml). alpha-TF had no effect on the protein amounts of tyrosinase, TRP (tyrosinase related protein)-1, and TRP-2 of human melanoma cells exposed to UV radiation, but inhibited tyrosine hydroxylase activity. alpha-TF neither directly inhibited tyrosinase activity of the large granule fraction extracted from melanoma cells, nor modulated glycosylation of tyrosinase. These results suggest that alpha-TF may be a candidate for whitening agent which suppresses melanogenesis, possibly by inhibiting tyrosine hydroxylase activity in an indirect manner. Further, alpha-TF decreased the amount of 8-hydroxydeoxyguanosine produced indirectly through active oxygen species (AOS) in guinea pig skin exposed to 2 times the minimal erythema dose of UVB radiation, but did not suppress the direct formation of cyclobutane pyrimidine dimers and (6-4) photoproducts. Thus alpha-TF may reduce AOS-induced DNA damage and thereby contribute at least in part to suppressing or retarding skin cancer development.

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