Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO<sub>4</sub>)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO<sub...

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Main Authors: Johanna Maria Hölken, Katja Friedrich, Russel Kerr, Nicole Elisabeth Teusch
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/6/245
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author Johanna Maria Hölken
Katja Friedrich
Russel Kerr
Nicole Elisabeth Teusch
author_facet Johanna Maria Hölken
Katja Friedrich
Russel Kerr
Nicole Elisabeth Teusch
author_sort Johanna Maria Hölken
collection DOAJ
description This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO<sub>4</sub>)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO<sub>4</sub>-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO<sub>4</sub>-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO<sub>4</sub>-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO<sub>4</sub>-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required.
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spelling doaj-art-0a48d3bdecbc4af9983efb71b3a975ae2025-08-20T03:27:37ZengMDPI AGMarine Drugs1660-33972025-06-0123624510.3390/md23060245Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin SensitizationJohanna Maria Hölken0Katja Friedrich1Russel Kerr2Nicole Elisabeth Teusch3Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, GermanyInstitute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, GermanyDepartment of Chemistry, Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, CanadaInstitute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, GermanyThis study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO<sub>4</sub>)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO<sub>4</sub>-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO<sub>4</sub>-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO<sub>4</sub>-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO<sub>4</sub>-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required.https://www.mdpi.com/1660-3397/23/6/245pseudopterosin<i>Antillogorgia elisabethae</i>skindermal dendritic cellsNiSO<sub>4</sub>dexamethasone
spellingShingle Johanna Maria Hölken
Katja Friedrich
Russel Kerr
Nicole Elisabeth Teusch
Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
Marine Drugs
pseudopterosin
<i>Antillogorgia elisabethae</i>
skin
dermal dendritic cells
NiSO<sub>4</sub>
dexamethasone
title Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
title_full Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
title_fullStr Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
title_full_unstemmed Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
title_short Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization
title_sort pseudopterosin a d modulates dendritic cell activation in skin sensitization
topic pseudopterosin
<i>Antillogorgia elisabethae</i>
skin
dermal dendritic cells
NiSO<sub>4</sub>
dexamethasone
url https://www.mdpi.com/1660-3397/23/6/245
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AT katjafriedrich pseudopterosinadmodulatesdendriticcellactivationinskinsensitization
AT russelkerr pseudopterosinadmodulatesdendriticcellactivationinskinsensitization
AT nicoleelisabethteusch pseudopterosinadmodulatesdendriticcellactivationinskinsensitization