<i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes

<i>Gentiana lutea</i> is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that <i>Gentiana lutea</i> extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigat...

Full description

Bibliographic Details
Main Authors: Fabian Gendrisch, Anna Nováčková, Michaela Sochorová, Birgit Haarhaus, Kateřina Vávrová, Christoph M. Schempp, Ute Wölfle
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/8/1832
_version_ 1797570516619362304
author Fabian Gendrisch
Anna Nováčková
Michaela Sochorová
Birgit Haarhaus
Kateřina Vávrová
Christoph M. Schempp
Ute Wölfle
author_facet Fabian Gendrisch
Anna Nováčková
Michaela Sochorová
Birgit Haarhaus
Kateřina Vávrová
Christoph M. Schempp
Ute Wölfle
author_sort Fabian Gendrisch
collection DOAJ
description <i>Gentiana lutea</i> is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that <i>Gentiana lutea</i> 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 (<i>CERS3</i>) and elongases (<i>ELOVL1</i> and <i>4</i>) 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 <i>DEFB4A</i>, as well as decreased expression of <i>ELOVL4</i>. The treatment with GE partly rescued the reduced expression of <i>ELOVL4</i> in psoriasis-like HPKs and augmented <i>CERS3</i> 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.
first_indexed 2024-03-10T20:25:41Z
format Article
id doaj.art-f1583c43ea7a4abdbd6f5690c7775758
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-10T20:25:41Z
publishDate 2020-04-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-f1583c43ea7a4abdbd6f5690c77757582023-11-19T21:49:51ZengMDPI AGMolecules1420-30492020-04-01258183210.3390/molecules25081832<i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like KeratinocytesFabian Gendrisch0Anna Nováčková1Michaela Sochorová2Birgit Haarhaus3Kateřina Vávrová4Christoph M. Schempp5Ute Wölfle6Department of Dermatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Breisgau, GermanySkin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, CZ-50005 Hradec Králové, Czech RepublicSkin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, CZ-50005 Hradec Králové, Czech RepublicDepartment of Dermatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Breisgau, GermanySkin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, CZ-50005 Hradec Králové, Czech RepublicDepartment of Dermatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Breisgau, GermanyDepartment of Dermatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Breisgau, Germany<i>Gentiana lutea</i> is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that <i>Gentiana lutea</i> 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 (<i>CERS3</i>) and elongases (<i>ELOVL1</i> and <i>4</i>) 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 <i>DEFB4A</i>, as well as decreased expression of <i>ELOVL4</i>. The treatment with GE partly rescued the reduced expression of <i>ELOVL4</i> in psoriasis-like HPKs and augmented <i>CERS3</i> 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.https://www.mdpi.com/1420-3049/25/8/1832ceramidesskin<i>Gentiana lutea</i>CerSELOVL
spellingShingle Fabian Gendrisch
Anna Nováčková
Michaela Sochorová
Birgit Haarhaus
Kateřina Vávrová
Christoph M. Schempp
Ute Wölfle
<i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
Molecules
ceramides
skin
<i>Gentiana lutea</i>
CerS
ELOVL
title <i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
title_full <i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
title_fullStr <i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
title_full_unstemmed <i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
title_short <i>Gentiana lutea</i> Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes
title_sort i gentiana lutea i extract modulates ceramide synthesis in primary and psoriasis like keratinocytes
topic ceramides
skin
<i>Gentiana lutea</i>
CerS
ELOVL
url https://www.mdpi.com/1420-3049/25/8/1832
work_keys_str_mv AT fabiangendrisch igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT annanovackova igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT michaelasochorova igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT birgithaarhaus igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT katerinavavrova igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT christophmschempp igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes
AT utewolfle igentianaluteaiextractmodulatesceramidesynthesisinprimaryandpsoriasislikekeratinocytes