{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T05:30:56Z","timestamp":1764739856794,"version":"3.46.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"MICIU\/AEI","doi-asserted-by":"publisher","award":["PID2023-147444OB-I00"],"award-info":[{"award-number":["PID2023-147444OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TOXICROP project","award":["H2020-823860"],"award-info":[{"award-number":["H2020-823860"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PRE2020-094412"],"award-info":[{"award-number":["PRE2020-094412"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023561","name":"Spanish Ministerio de Universidades","doi-asserted-by":"crossref","award":["FPU2019-01247"],"award-info":[{"award-number":["FPU2019-01247"]}],"id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Lichens are complex symbiotic systems known for synthesizing diverse secondary metabolites with documented antimicrobial, antioxidant, and antiproliferative activities. The present study focused on Pseudevernia furfuracea, a species widely distributed across Moroccan habitats. Two hydrodistillation-derived extracts (HE1 and HE2) were analyzed through ultra-high-Performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS\/MS) to characterize their metabolite composition, and their effects were evaluated on Jurkat cells, a representative human cell line of the immune system. As the results of the characterization, the main compounds identified were Caprolactam, N,N-Diethylaniline, Erucamide, and 4-Isopropylaniline. Cytotoxicity assessment revealed that both HE1 and HE2 decreased the viability of Jurkat cells in a concentration-dependent manner. The mean effective concentrations (EC50) after 24 h of treatment were 53.79 \u00b1 2.92 \u00b5g\/mL for HE1 and 59.76 \u00b1 2.01 \u00b5g\/mL for HE2. Cell death mechanisms were further examined by flow cytometry, revealing that apoptosis predominated after 24 h of treatment, progressing mainly to late apoptotic stages after 48 h. In parallel, the expression levels of key cytokine genes, including IL-2, TNF-\u03b1, and IFN-\u03b3, were quantified at the mRNA level to evaluate potential immunomodulatory effects. Up-regulation was observed in IL-2 after exposure to both extracts for 24 and 48 h, and in the case of IFN-\u03b3 after exposure to HE2 for 24 h; in contrast, HE1 and HE2 produced down-regulation in TNF-\u03b1 at 24 h. These findings suggest that HE1 and HE2 have immunomodulatory activity in Jurkat cells. Further investigations are needed to elucidate the underlying mechanisms and to clarify how HE1 and HE2 influence immune responses in human systems.<\/jats:p>","DOI":"10.3390\/jox15060201","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Profiling and In Vitro Assessment of the Immunomodulatory Effects of Hydrodistillation-Derived Extracts from the Fruticose Lichen Pseudevernia furfuracea (L.) Zopf. on Human Lymphocytes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4846-0075","authenticated-orcid":false,"given":"Yasser","family":"Essadki","sequence":"first","affiliation":[{"name":"Water Sciences, Microbial Biotechnologies and Sustainability of Natural Resources Laboratory (Aquabiotech), Faculty of Sciences Semlalia of Marrakech, Cadi Ayyad University, UCA, Av. Prince My Abdellah, P.O. Box 2390, Marrakech 40000, Morocco"}]},{"given":"Antonio","family":"Casas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C. Tramontana, 2, 41012 Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9162-7236","authenticated-orcid":false,"given":"Antonio","family":"Cascajosa-Lira","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C. Tramontana, 2, 41012 Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-9287","authenticated-orcid":false,"given":"Leticia","family":"Diez-Quijada","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C. Tramontana, 2, 41012 Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-885X","authenticated-orcid":false,"given":"Alexandre","family":"Campos","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto (FCUP), Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2922-8020","authenticated-orcid":false,"given":"Fatima","family":"El Khalloufi","sequence":"additional","affiliation":[{"name":"Natural Resources Engineering and Environmental Impacts Team, Multidisciplinary Research and Innovation Laboratory, Polydisciplinary Faculty of Khouribga, Sultan Moulay Slimane University of Beni Mellal, Bd 2 Mars, Khouribga 25000, Morocco"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-9637","authenticated-orcid":false,"given":"Brahim","family":"Oudra","sequence":"additional","affiliation":[{"name":"Water Sciences, Microbial Biotechnologies and Sustainability of Natural Resources Laboratory (Aquabiotech), Faculty of Sciences Semlalia of Marrakech, Cadi Ayyad University, UCA, Av. Prince My Abdellah, P.O. Box 2390, Marrakech 40000, Morocco"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1524-748X","authenticated-orcid":false,"given":"Ana M.","family":"Came\u00e1n","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C. Tramontana, 2, 41012 Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-3294","authenticated-orcid":false,"given":"Angeles","family":"Jos","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C. Tramontana, 2, 41012 Sevilla, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Yasmin, F., and Jabin, R. (2024). Physiology of Lichen. 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