Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis.

• MeSH
• Ceramides metabolism   MeSH
• Fatty Acid Elongases genetics   metabolism   MeSH
• Gentiana chemistry   MeSH
• Keratinocytes cytology   drug effects   metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Lipid Metabolism drug effects   MeSH
• Eye Proteins genetics   metabolism   MeSH
• Primary Cell Culture MeSH
• Psoriasis genetics   metabolism   MeSH
• Gene Expression Regulation drug effects   MeSH
• Plant Extracts chemistry   pharmacology   MeSH
• Sphingosine N-Acyltransferase genetics   metabolism   MeSH
• Case-Control Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH