Abstract
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.
Highlights
The outermost layer of the human skin, the stratum corneum (SC), protects the body against excessive water loss and penetration of undesired substances from the environment [1]
We analyzed if the concentrations of ceramides, glucosylceramides and sphingomyelin in human primary keratinocytes (HPKs) could be increased by Gentiana lutea extract (GE)
Considering the individual ceramide subclasses, ceramides AS/AdS, which have sphingosine or dihydrosphingosine amide-linked to an α-hydroxy fatty acids (FA), were increased ~7-fold by GE (Figure 1d)
Summary
The outermost layer of the human skin, the stratum corneum (SC), protects the body against excessive water loss and penetration of undesired substances from the environment [1]. The SC consists of dead cells, corneocytes, filled with keratins and an extracellular lipid matrix. These multiple lipid lamellae are essential for a correct epidermal permeability barrier [2,3] and contain mainly ceramides (approximately 50% of the SC lipids), as well as cholesterol and free fatty acids (FA). The skin barrier ceramides are a highly heterogeneous lipid class and they differ in their polar head structure, chain length, hydroxylation and esterification pattern [4,5]. Ceramide levels are reduced in psoriatic epidermis compared to healthy skin, which correlates with an increased transepidermal water loss (TEWL) [10,11]; reviewed in [12].
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