{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:43:02Z","timestamp":1782877382699,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministero dell\u2019Istruzione dell\u2019Universit\u00e0"},{"name":"PhD fellowship of the University of Trieste"},{"name":"ProRett research ONLUS (Italy)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study investigates the bioactive properties of different extracts of cardoon leaves in rescuing neuronal development arrest in an in vitro model of Rett syndrome (RTT). Samples were obtained from plants harvested at different maturity stages and extracted with two different methodologies, namely Naviglio\u00ae and supercritical carbon dioxide (scCO2). While scCO2 extracts more hydrophobic fractions, the Naviglio\u00ae method extracts phenolic compounds and less hydrophobic components. Only the scCO2 cardoon leaves extract obtained from plants harvested in spring induced a significant rescue of neuronal atrophy in RTT neurons, while the scCO2 extract from the autumn harvest stimulated dendrite outgrowth in Wild-Type (WT) neurons. The scCO2 extracts were the richest in squalene, 3\u00df-taraxerol and lupeol, with concentrations in autumn harvest doubling those in spring harvest. The Naviglio\u00ae extract was rich in cynaropicrin and exerted a toxic effect at 20 \u00b5M on both WT and RTT neurons. When cynaropicrin, squalene, lupeol and 3\u00df-taraxerol were tested individually, no positive effect was observed, whereas a significant neurotoxicity of cynaropicrin and lupeol was evident. In conclusion, cardoon leaves extracts with high content of hydrophobic bioactive molecules and low cynaropicrin and lupeol concentrations have pharmacological potential to stimulate neuronal development in RTT and WT neurons in vitro.<\/jats:p>","DOI":"10.3390\/molecules27248772","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:34:20Z","timestamp":1670819660000},"page":"8772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neuroprotective Properties of Cardoon Leaves Extracts against Neurodevelopmental Deficits in an In Vitro Model of Rett Syndrome Depend on the Extraction Method and Harvest Time"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0908-1196","authenticated-orcid":false,"given":"Mariachiara","family":"Spennato","sequence":"first","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-5262","authenticated-orcid":false,"given":"Ottavia Maria","family":"Roggero","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3054-3375","authenticated-orcid":false,"given":"Simona","family":"Varriale","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University Federico II of Naples, Via Cinthia, 4, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8281-8038","authenticated-orcid":false,"given":"Fioretta","family":"Asaro","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2227-7935","authenticated-orcid":false,"given":"Angelo","family":"Cortesi","sequence":"additional","affiliation":[{"name":"Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio 6\/A, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1334-7201","authenticated-orcid":false,"given":"Jan","family":"Ka\u0161par","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-0603","authenticated-orcid":false,"given":"Enrico","family":"Tongiorgi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, Via L. 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