Ionic composition of Shotokuseki extract alters cell differentiation and lipid metabolism in three-dimensional cultured human epidermis

Corneocytes and intercellular lipids form the stratum corneum. The content and composition of intercellular lipids in the stratum corneum significantly affect skin barrier function. The purpose of this study was to demonstrate the effect of Shotokuseki extract (SE) on intercellular lipid production and metabolism in human three-dimensional cultured human epidermis. SE or ion mixtures containing five common ions were applied to three-dimensional cultured human epidermis for 2–8 days for each assay. The mRNA expression levels of epidermal differentiation markers and lipid metabolism genes were quantified by real-time PCR. After extraction of lipids from the epidermis, ceramide, sphingosine, free fatty acids, and cholesterol were quantified by LC-MS/MS, GC-MS, or HPLC. The results showed that the application of SE increased the gene expression levels of epidermal differentiation markers keratin10 and transglutaminase. Elongation of very long-chain fatty acids protein 3, serine palmitoyl transferase, ceramide synthase 3, and acid ceramidase mRNA expression levels increased and fatty acid synthase mRNA expression decreased. The content of each lipid, [EOS] ceramide decreased and total sphingosine content increased on day 4. On day 8 of application, ceramide [NDS], [NP], and [EODS] increased and total free fatty acid content decreased. These results show that SE alters the lipid composition of the epidermis, increasing ceramides and decreasing free fatty acids in the epidermis. The composition of the ions in the SE may be responsible for the changes in lipid composition. These behaviors were different from those observed when the ion mixture was applied.

Graphical abstract