A reduced lipid content in the stratum corneum is a major cause of skin barrier function deterioration in various diseases. Accordingly, the promotion of lipid production is a potential strategy to improve skin barrier function. Recent studies support the beneficial effects of adiponectin on lipid metabolism and senescence in keratinocytes. We screened plant extracts that enhance the lipid synthesis of keratinocytes via sirt1-nuclear hormone receptor signaling in the adiponectin pathway. The levels of major lipid synthesis enzymes and transcription factors as well as sphingolipids, involved in adiponectin-associated keratinocyte lipid production, were evaluated in plant extracts or the adiponectin-treated human epidermal equivalent. The mRNA expression levels of fatty acid synthase, HMG-CoA reductase, and serine palmitoyl transferase were increased in the extracts of fruits of Lycium barbarum L., Prunus tomentosa, and Melia toosendan among 20 extracts from treated plants. The transcription factors SIRT1, LXRα, PPARs, and SREBP were also upregulated. The levels of ceramide and its downstream sphingolipid metabolites were significantly increased. Expression levels of keratinocyte differentiation markers were also increased. In particular, among the extracts with a detectable effect, Melia toosendan fructus showed the highest expression of lipid synthase. These results indicate that the Melia toosendan fructus extract is an appropriate material for improving skin barrier function.

Screening of a phytochemical library for the identification of sirt1-dependent lipid synthesis effects in keratinocytes