Yushi Katsuyama

Skin sensitivity is a serious problem for many people, and it can be induced by various factors such as UV irradiation, physical and mental stresses, air pollution, dry air and so on. Skin dryness triggered by UV and dry air is one of the most important causes inducing the development of sensitive skin, and it has been reported that oxidative stress contributes to skin dryness. In this study, we investigated whether treatment with 3‐O‐laurylglyceryl ascorbate (VC‐3LG), which is an amphipathic ascorbic acid derivative, can suppress the development of sensitive skin. The results demonstrate that VC‐3LG restores the expression levels of interleukin‐1α, nerve growth factor and matrix metalloprotease‐9 in the dry skin models of reconstructed human epidermal equivalents (RHEEs) and in H₂O₂‐treated keratinocytes. In addition, VC‐3LG suppresses the dendrite elongation of nerve cells induced in RHEEs by dry skin conditions and by H₂O₂ treatment of keratinocytes. Therefore, we consider that treatment of the skin with VC‐3LG is an effective approach to improve the development of sensitive skin.

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L-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C–alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1–28) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure–function relationships. Although not the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid (6, IC₅₀ = 81.4 µM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20, IC₅₀ = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl-derivatives (2–14) exhibit stronger inhibitory activity than the corresponding 2-O-alkyl-derivatives (16–28); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.

Summary: Background: Ascorbic acid (AsA) has multifunctional benefits on skin beauty, such as the reduction in oxidative stress and the induction of collagen production. Among them, the prevention and improvement of skin pigmentation by AsA is a most important benefit for people. However, it is well known that AsA not only is quite unstable in formulations but it also has a low capability of skin penetration due to its hydrophilic property. In addition, existing water‐soluble AsA derivatives that were developed to improve its stability also have low skin penetration.Aim: To investigate the potential of a newly synthesized amphiphilic derivative of AsA, 3‐O‐Glyceryl‐2‐O‐hexyl ascorbate (VC‐HG), which has an added glyceryl group and a hexyl group, on skin beauty focusing on its skin lightening/whitening effects.Methods: DNA microarray analysis and real‐time PCR were used to clarify the effects of VC‐HG on melanogenesis using B16 mouse melanoma cells. The effects of VC‐HG on melanin synthesis, tyrosinase protein levels, and the inhibition of tyrosinase activity were evaluated.Results: DNA microarray analysis revealed that treatment with VC‐HG downregulated the expression of genes encoding tyrosinase and MyosinVa. Further, real‐time PCR analysis showed the downregulation of tyrosinase, MyosinVa, Rab27a, and Kinesin mRNAs following VC‐HG treatment. In addition, VC‐HG caused decreases in tyrosinase protein levels and melanin synthesis.Conclusion: We conclude that VC‐HG has an impact on skin lightening/whitening by inhibiting tyrosinase protein synthesis and interfering with intracellular melanosome transport.

Objective: A higher trans‐epidermal water loss (TEWL) occurs in rough skin, in elder skin and also in atopic dermatitis. An impaired skin barrier function is considered to be caused by an incomplete construction of the intercellular lamellar structure due to the quantitative reduction of ceramides. Since these symptoms coexist with oxidative stress, we hypothesized that impairment of the skin barrier function is accelerated by oxidative stress. Thus, the purpose of this study was to clarify the effect of oxidative stress on ceramide synthesis and to characterize whether antioxidants can improve skin barrier function. 3‐O‐Laurylglyceryl ascorbate (VC‐3LG), which is a newly amphipathic derivative of ascorbic acid, was evaluated as a candidate antioxidant.Methods: We characterized the mRNA expression levels of serine palmitoyltransferase (SPT) in normal human epidermal keratinocytes (NHEKs) treated with H₂O₂ using real‐time PCR analysis. In order to evaluate the effect of VC‐3LG on skin barrier function, we used several assays with reconstructed human epidermis equivalents (RHEEs).Results: Ceramide synthesis was down‐regulated in NHEKs by oxidative stress. Treatment with VC‐3LG abrogated the down‐regulation of SPT mRNA in NHEKs caused by oxidative stress, and stimulated SPT mRNA expression levels. In experiments characterizing the antioxidative properties of VC‐3LG, VC‐3LG reduced oxidative stress in NHEKs by up‐regulating catalase mRNA expression. In addition, VC‐3LG stimulated the skin barrier function in RHEEs, which had lower TEWL values compared with untreated RHEEs. Furthermore, VC‐3LG increased the quantity of ceramide in RHEEs.Conclusion: Taken together, we conclude that VC‐3LG reinforces the skin barrier function due to its reduction of oxidative stress and its promotion of ceramide synthesis.