Hölken Johanna Maria, Friedrich Katja, Kerr Russel, Teusch Nicole Elisabeth
Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Department of Chemistry, Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Mar Drugs. 2025 Jun 10;23(6):245. doi: 10.3390/md23060245.
This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO-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-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-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-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.
本研究调查了海洋二萜糖苷类假蕨素A-D（PsA-D）在减轻硫酸镍（NiSO）诱导的皮肤致敏中的抗炎作用。在真皮树突状细胞（DDC）替代物中，PsA-D预处理显著降低了NiSO诱导的关键激活表面标志物、分化簇（CD）54（约1.2倍）和CD86（约1.6倍）的上调。此外，PsA-D通过抑制κBα抑制剂（IκBα）降解，抑制了NiSO诱导的活化B细胞核因子κB轻链增强子（NF-κB）通路的激活。此外，PsA-D通过抑制NiSO诱导的促炎细胞因子分泌来抑制炎症反应，这些促炎细胞因子包括白细胞介素（IL）-8（约6.8倍）、IL-6（约2.2倍）和IL-1β（约5.3倍）。在包含DDC替代物的全层人类皮肤模型中，局部应用PsA-D有效减弱了NiSO诱导的IL-8（约2.1倍）、IL-6（约2.6倍）和IL-1β（约2.2倍）的mRNA表达，以及关键炎症介质环氧合酶-2（COX-2）（约3.5倍）和含NOD样受体家族pyrin结构域3（NLRP3）（约2.1倍）。总体而言，PsA-D表现出与基准皮质类固醇地塞米松相当的疗效，为治疗皮肤致敏和过敏性接触性皮炎提供了一种有前景的皮质类固醇替代疗法。然而，为了最大限度地发挥PsA-D的治疗潜力，需要对优化PsA-D的生物利用度和制剂进行进一步研究。
