Abstract
The activation of peroxisomeproliferator-activated receptor (PPAR) α can stimulate the expression of ceramide-related enzymes, and a major component of strawberry seed extract (SSE) tiliroside enhances the expression of PPARα. We determined whether SSE and tiliroside may stimulate ceramide synthesis in the stratum corneum (SC) of the human epidermal equivalents (HEEs) culture model. Treatment with SSE at 1.0 and 3.0 μg/mL elicited a significant increase in the total ceramide content in the SC, which was accompanied by a significant increase in almost all ceramide species except for ceramide [EOS] and [AP]. Treatment with tiliroside at 0.3 μg/mL slightly accentuated the total ceramide content in the SC together with a significant increase in the ceramide [NS, NDS] content. Messenger RNA analysis demonstrated that SSE at 1 or 3 μg/mL significantly stimulated the gene expression of serine palmitoyltransferase (SPT) 2, ceramide synthase (CerS) 3, glucosylceramide synthase (GCS), and β-glucocerebrosidase (GBA) but not of SPT1, sphingomyelin synthase (SMS) 1/2 and acid sphingomyelinase (ASM). In contrast, tiliroside elicited significant increases in the gene expression levels of GCS and GBA only at 0.3 and/or 0.1 μg/mL. Western blotting analysis revealed that both SSE and tiliroside enhanced the protein expression levels of GCS and GBA but not of SPT2 at 1 or 3 and 0.1 or 0.3 μg/mL, respectively. These findings suggested that both SSE and tiliroside have a distinct potential to stimulate the level of ceramide [NS, NDS] in the SC by enhancing the expression of GCS and GBA. The higher stimulatory effect with SSE than tiliroside on SC ceramide synthesis correlates with the significant increase observed with SSE but not tiliroside in the gene expression levels of SPT2 and CerS3. Therefore, it is anticipated that SSE is effective in improving skin barrier function and moisture retention in several ceramide-deficit skin conditions, including surfactant-induced roughened skin, xerosis, and atopic dermatitis.
Highlights
Ceramides are a type of sphingolipid and consist of a sphingoid base and a saturated fatty acid moiety
Quantitative analysis of ceramide revealed that treatment with strawberry seed extract (SSE) at concentrations of 1 and 3 μg/mL elicited a significant increase in the total ceramide content in the stratum corneum (SC) of the treated 3-dimensional human epidermal equivalents (3DHEEs) (Fig 2A), which was accompanied by a significant increase in almost all the ceramide species (Fig 2B/2C) except for [EOS] and [AP]
The role of each ceramide species has not been clearly studied, acylceramides such as ceramide [EOS] and [EOH] is well known to be more distinctly associated with barrier function in SC than the other ceramides [2]
Summary
Ceramides are a type of sphingolipid and consist of a sphingoid base and a saturated fatty acid moiety. For amelioration of such dry skin conditions, it is important to compensate with orally or topically administered natural ceramide or by stimulating synthesis of ceramide in dry skin with xerosis and atopic dermatitis. Topical application of synthetic pseudo-ceramide has already been established as a means to efficiently ameliorate dry skin in xerosis and atopic dermatitis [12,13,14,15,16,17,18,19]. Because of limitations in such topical application of ceramide in terms of its applied concentration and duration of efficacy, it could be more efficient to perform daily oral administration of food materials capable of stimulating ceramide synthesis, which results in an increase in ceramide mass in the SC
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