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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MDPI AG
2025-06-01
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| 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 |
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| 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| 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 |
| work_keys_str_mv | AT johannamariaholken pseudopterosinadmodulatesdendriticcellactivationinskinsensitization AT katjafriedrich pseudopterosinadmodulatesdendriticcellactivationinskinsensitization AT russelkerr pseudopterosinadmodulatesdendriticcellactivationinskinsensitization AT nicoleelisabethteusch pseudopterosinadmodulatesdendriticcellactivationinskinsensitization |