{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:49:09Z","timestamp":1768812549657,"version":"3.49.0"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xeda International S.A.S.","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Xeda International S.A.S.","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Xeda International S.A.S.","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Italian Ministry for Research, RFO funds","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Italian Ministry for Research, RFO funds","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Italian Ministry for Research, RFO funds","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Foundation for Science and Technology (FCT, Portugal) projects","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Foundation for Science and Technology (FCT, Portugal) projects","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Foundation for Science and Technology (FCT, Portugal) projects","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Foundation for Science and Technology (FCT) for a PhD grant","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Foundation for Science and Technology (FCT) for a PhD grant","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Foundation for Science and Technology (FCT) for a PhD grant","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to investigate \u03b2-Caryophyllene (BCA) pharmacokinetics as well as the potential antitumor activity and mechanism of action of BCA and eugenol (EU), alone or in combination, in U87 glioblastoma (GB) cells. The BCA pharmacokinetic was studied by evaluating its concentration profiles in rat blood and cerebrospinal fluid after oral and intravenous administration. EU and BCA antitumor mechanisms were assessed by comparing their effects in U87 GB cells and non-tumoral HMC3 cells. Cell death, cell cycle regulation and mitochondrial membrane potential (MMP) were evaluated using flow cytometry. mRNA levels of target genes were evaluated by qPCR. Secreted cytokines were measured by Luminex\u00ae. BCA, as well as EU, permeates the brain. EU and BCA affected the viability and proliferation of U87 cells (up to 50%, p &lt; 0.001) but not HMC3 cells and showed a synergistic effect. BCA and EU induced G0\/G1 cell cycle arrest, increasing apoptosis\/necrosis. EU and BCA induced the downregulation of mRNAs encoding for key proteins involved in GB angiogenesis (VEGFA decreased op to 60%, p &lt; 0.01), proliferation and progression, and showed anti-inflammatory activity (IL-4 significantly decreased, p &lt; 0.001). EU and BCA demonstrated strong and multitarget antitumor activity in U87 cells. Our results provide a strong rationale for the further evaluation of EU and BCA as possible therapeutic molecules in GB management.<\/jats:p>","DOI":"10.3390\/ijms26010238","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:51:57Z","timestamp":1735631517000},"page":"238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clove Essential Oil as a Source of Antitumoral Compounds Capable of Crossing the Blood\u2013Brain Barrier: A Focus on the Effects of \u03b2-Caryophyllene and Eugenol in a Glioblastoma Cell Line"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-7536","authenticated-orcid":false,"given":"Renato","family":"Spigarelli","sequence":"first","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8525-2981","authenticated-orcid":false,"given":"Enzo","family":"Spisni","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-1611","authenticated-orcid":false,"given":"Mariana","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-6683","authenticated-orcid":false,"given":"C\u00e9lia","family":"Cabral","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"iCBR, Group of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-7089","authenticated-orcid":false,"given":"Ilaria Maria","family":"Saracino","sequence":"additional","affiliation":[{"name":"Microbiology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2942-1437","authenticated-orcid":false,"given":"Giada","family":"Botti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, 44121 Ferrara, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6648-2562","authenticated-orcid":false,"given":"Alessandro","family":"Dalpiaz","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, 44121 Ferrara, Italy"}]},{"given":"Sarah","family":"Beggiato","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara and LTTA Center, Via Fossato di Mortara 19, 44121 Ferrara, Italy"}]},{"given":"Maria Chiara","family":"Valerii","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/neuonc\/noaa200","article-title":"CBTRUS 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