{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:35:28Z","timestamp":1774485328226,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bundesministerium f\u00fcr Ern\u00e4hrung und Landwirtschaft (BMEL)","award":["281A308C18"],"award-info":[{"award-number":["281A308C18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO4)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO4-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 NiSO4-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) pathway by suppressing inhibitor of kappa B alpha (I\u03baB\u03b1) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO4-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1\u03b2 (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO4-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1\u03b2 (~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\u2019s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required.<\/jats:p>","DOI":"10.3390\/md23060245","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T06:48:56Z","timestamp":1749538136000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pseudopterosin A-D Modulates Dendritic Cell Activation in Skin Sensitization"],"prefix":"10.3390","volume":"23","author":[{"given":"Johanna Maria","family":"H\u00f6lken","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russel","family":"Kerr","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-1493","authenticated-orcid":false,"given":"Nicole Elisabeth","family":"Teusch","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1021\/np049802o","article-title":"New Pseudopterosin and Seco-Pseudopterosin Diterpene Glycosides from Two Colombian Isolates of Pseudopterogorgia Elisabethae and Their Diverse Biological Activities","volume":"67","author":"Shi","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5140","DOI":"10.1021\/jo00376a016","article-title":"The Pseudopterosins: A New Class of Antiinflammatory and Analgesic Diterpene Pentosides from the Marine Sea Whip Pseudopterogorgia Elisabethae (Octocorallia)","volume":"51","author":"Look","year":"1986","journal-title":"J. Org. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1073\/pnas.83.17.6238","article-title":"The Pseudopterosins: Anti-Inflammatory and Analgesic Natural Products from the Sea Whip Pseudopterogorgia Elisabethae","volume":"83","author":"Look","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1016\/j.bmc.2011.06.083","article-title":"Marine Diterpene Glycosides","volume":"19","author":"McCulloch","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/hlca.200490099","article-title":"New Antibacterial Diterpenes from Pseudopterogorgia Elisabethae","volume":"87","author":"Ata","year":"2004","journal-title":"Helv. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1021\/jo00303a030","article-title":"New Anti-Inflammatory Pseudopterosins from the Marine Octocoral Pseudopterogorgia Elisabethae","volume":"55","author":"Roussis","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1016\/S0040-4020(03)00515-5","article-title":"Identification of Anti-Inflammatory Diterpenes from the Marine Gorgonian Pseudopterogorgia Elisabethae","volume":"59","author":"Ata","year":"2003","journal-title":"Tetrahedron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10627","DOI":"10.1016\/j.tet.2004.09.017","article-title":"Pseudopterosins P\u2013V, New Compounds from the Gorgonian Octocoral Pseudopterogorgia Elisabethae from Providencia Island, Colombian Caribbean","volume":"60","author":"Duque","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3390\/md9030334","article-title":"Cytotoxic and Antimicrobial Activity of Pseudopterosins and Seco-Pseudopterosins Isolated from the Octocoral Pseudopterogorgia Elisabethae of San Andr\u00e9s and Providencia Islands (Southwest Caribbean Sea)","volume":"9","author":"Correa","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2300390","DOI":"10.1002\/pmic.202300390","article-title":"Mechanism of Action of Pseudopteroxazole and Pseudopterosin G: Diterpenes from Marine Origin","volume":"24","author":"Janzing","year":"2024","journal-title":"Proteomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"PL401","DOI":"10.1016\/S0024-3205(98)00229-X","article-title":"Pharmacological Characterization of the Pseudopterosins: Novel Anti-Inflammatory Natural Products Isolated from the Caribbean Soft Coral, Pseudopterogorgia Elisabethae","volume":"62","author":"Mayer","year":"1998","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sperlich, J., Kerr, R., and Teusch, N. (2017). The Marine Natural Product Pseudopterosin Blocks Cytokine Release of Triple-Negative Breast Cancer and Monocytic Leukemia Cells by Inhibiting Nf-\u039ab Signaling. Mar. Drugs, 15.","DOI":"10.3390\/md15090262"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sperlich, J., and Teusch, N. (2018). Pseudopterosin Inhibits Proliferation and 3d Invasion in Triple-Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha. Molecules, 23.","DOI":"10.20944\/preprints201807.0224.v1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Xie, B., H\u00e4nsel, J., Mundorf, V., Betz, J., Reimche, I., Erkan, M., B\u00fcdeyri, I., Gesell, A., Kerr, R.G., and Ariantari, N.P. (2020). Pseudopterosin and O-Methyltylophorinidine Suppress Cell Growth in a 3d Spheroid Co-Culture Model of Pancreatic Ductal Adenocarcinoma. Bioengineering, 7.","DOI":"10.3390\/bioengineering7020057"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1096\/fasebj.2021.35.S1.04601","article-title":"Therapeutic Potential of Pseudopterosin H on a Prostate Cancer Cell Line","volume":"35","author":"Bowers","year":"2021","journal-title":"FASEB J."},{"key":"ref_16","unstructured":"Haimes, H.B., and Jimenez, P.A. (1997). Use of Pseudopterosin for Promoting Wound Healing. (5,597,808), U.S. Patent."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.3390\/md11093258","article-title":"Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin a Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells","volume":"11","author":"Day","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"A427","DOI":"10.1096\/fasebj.21.5.A427-d","article-title":"Mechanism of Action of the Pseudopterosins and Their Role in Wound Healing","volume":"21","author":"Moya","year":"2007","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"729.7","DOI":"10.1096\/fasebj.22.1_supplement.729.7","article-title":"Pseudopterosins Appear to Enhance the Wound Healing Process through an Adenosine Receptor Mediated Mechanism","volume":"22","author":"Moya","year":"2008","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tips.2010.02.005","article-title":"The Odyssey of Marine Pharmaceuticals: A Current Pipeline Perspective","volume":"31","author":"Mayer","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1021\/cen-v073n047.p042","article-title":"Supply Issues Complicate Trek of Chemicals from Sea to Market","volume":"73","author":"Rouhi","year":"1995","journal-title":"Chem. Eng. News"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3733\/ca.v051n04p45","article-title":"Sea Grant Seeks New Drugs from the Sea","volume":"51","author":"Fenical","year":"1997","journal-title":"Calif. Agric."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mcna.2019.08.012","article-title":"Allergic Contact Dermatitis","volume":"104","author":"Nassau","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/cod.14073","article-title":"Regulation of the Immune Response to Contact Sensitizers by Nrf2","volume":"87","author":"Vallion","year":"2022","journal-title":"Contact Dermat."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sebasti\u00e3o, A.I., Ferreira, I., Brites, G., Silva, A., Neves, B.M., and Teresa Cruz, M. (2020). Nlrp3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090867"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0887-2333(03)00019-5","article-title":"Analysis of Interleukin-1alpha (Il-1alpha) and Interleukin-8 (Il-8) Expression and Release in in Vitro Reconstructed Human Epidermis for the Prediction of in Vivo Skin Irritation and\/or Sensitization","volume":"17","author":"Coquette","year":"2003","journal-title":"Toxicol. In Vitro"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/sj.jid.5700819","article-title":"Activation of the Il-1beta-Processing Inflammasome Is Involved in Contact Hypersensitivity","volume":"127","author":"Watanabe","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1620\/tjem.184.159","article-title":"Maturation of Dendritic Cells Induced by Cytokines and Haptens","volume":"184","author":"Aiba","year":"1998","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0300-483X(99)00145-6","article-title":"Epidermal Cytokines in Experimental Contact Dermatitis","volume":"142","author":"Corsini","year":"2000","journal-title":"Toxicology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/tra.12026","article-title":"Presentation of Phagocytosed Antigens by Mhc Class I and Ii","volume":"14","author":"Mantegazza","year":"2013","journal-title":"Traffic"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/intimm\/dxae050","article-title":"The Role of Dendritic Cells in the Instruction of Helper T Cells in the Allergic March","volume":"36","author":"Kubo","year":"2024","journal-title":"Int. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1600-0536.2008.01443.x","article-title":"Dendritic Cells: Biology of the Skin","volume":"60","author":"Toebak","year":"2009","journal-title":"Contact Dermat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1093\/toxsci\/kfm178","article-title":"Nf-Kappab Plays a Major Role in the Maturation of Human Dendritic Cells Induced by Niso(4) but Not by Dncb","volume":"99","author":"Ade","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1523-1747.2003.12065.x","article-title":"P38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinases Play Distinct Roles in the Activation of Dendritic Cells by Two Representative Haptens, Nicl2 and 2,4-Dinitrochlorobenzene","volume":"120","author":"Aiba","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Reichardt, S.D., Amouret, A., Muzzi, C., Vettorazzi, S., Tuckermann, J.P., L\u00fchder, F., and Reichardt, H.M. (2021). The Role of Glucocorticoids in Inflammatory Diseases. Cells, 10.","DOI":"10.3390\/cells10112921"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2005.01.010","article-title":"Adverse Effects of Topical Glucocorticosteroids","volume":"54","author":"Hengge","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/jdv.20041","article-title":"Topical Corticosteroids in the Era of New Topical Therapies: Balancing Efficacy and Safety for Long-Term Use","volume":"38","author":"Egeberg","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1021\/jo801432t","article-title":"Synthesis and an Evaluation of the Bioactivity of the C-Glycoside of Pseudopterosin a Methyl Ether","volume":"73","author":"Zhong","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8324","DOI":"10.1016\/j.bmc.2010.09.067","article-title":"Synthetic Pseudopterosin Analogues: A Novel Class of Antiinflammatory Drug Candidates","volume":"18","author":"Flachsmann","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1021\/np50090a001","article-title":"Phospholipase A2 Inhibitors from Marine Organisms","volume":"55","author":"Potts","year":"1992","journal-title":"J. Nat. Prod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1034\/j.1600-051X.1999.260408.x","article-title":"Influence of Oas-1000 on Mediators of Inflammation","volume":"26","author":"Scherl","year":"1999","journal-title":"J. Clin. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"H\u00f6lken, J.M., Friedrich, K., Merkel, M., Blasius, N., Engels, U., Buhl, T., Mewes, K.R., Vierkotten, L., and Teusch, N.E. (2023). A Human 3d Immune Competent Full-Thickness Skin Model Mimicking Dermal Dendritic Cell Activation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1276151"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-9255-6-5","article-title":"Anti-Inflammatory Effects of the Gorgonian Pseudopterogorgia Elisabethae Collected at the Islands of Providencia and San Andr\u00e9s (Sw Caribbean)","volume":"6","author":"Correa","year":"2009","journal-title":"J. Inflamm."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Biernacki, M., and Skrzydlewska, E. (2025). Metabolic Pathways of Eicosanoids\u2014Derivatives of Arachidonic Acid and Their Significance in Skin. Cell. Mol. Biol. Lett., 30.","DOI":"10.1186\/s11658-025-00685-y"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0041-008X(03)00301-6","article-title":"Cyclooxygenases in the Skin: Pharmacological and Toxicological Implications","volume":"192","author":"Lee","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/carcin\/19.5.723","article-title":"Cox-2 Expression Is Induced by Uvb Exposure in Human Skin: Implications for the Development of Skin Cancer","volume":"19","author":"Buckman","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1038\/sj.bjp.0702866","article-title":"Distribution and Regulation of Cyclooxygenase-2 in Carrageenan-Induced Inflammation","volume":"128","author":"Nantel","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1208\/s12249-019-1582-x","article-title":"Approaches for Delivery of Drugs Topically","volume":"21","author":"Murthy","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"H\u00f6lken, J.M., and Teusch, N. (2023). The Monocytic Cell Line Thp-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021452"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"H\u00f6lken, J.M., Wurz, A.-L., Friedrich, K., B\u00f6ttcher, P., Asskali, D., Stark, H., Breitkreutz, J., Buhl, T., Vierkotten, L., and Mewes, K.R. (2024). Incorporating Immune Cell Surrogates into a Full-Thickness Tissue Equivalent of Human Skin to Characterize Dendritic Cell Activation. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-81014-9"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/6\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:21Z","timestamp":1760032161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/6\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["md23060245"],"URL":"https:\/\/doi.org\/10.3390\/md23060245","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}