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and anti-inflammatory effects. This study aims to optimize the supercritical fluid extraction process for recovering these high-value compounds from rice bran with improved bioactivity. A Central Composite Face-Centered Design was employed to optimize the extraction process by varying the temperature (40\u201380 \u00b0C) and pressure (200\u2013500 bar). The optimal extraction conditions were identified at 500 bar and 62 \u00b0C that led to the extraction of 17.3% mass yield with 784.5 mg of fatty acids and 36.6 mg of \u03b3-oryzanol per gram of extract, striking a balance between extraction yield and bioactive concentrations. When compared with conventional extractions with n-hexane, supercritical fluid extraction showed similar global yield (18.0 vs. 17.3%) and FA concentration (130.14 vs. 135.70 mg\/g of RB) but higher selectivity and extraction yield for \u03b3-oryzanol (18.0 vs. 36.4 mg\/g extract; 3.3 vs. 6.3 mg\/g of RB). Cellular antioxidant activity assays showed that both extracts reduced the quantity of reactive oxygen species (ROS) up to 50% in Caco-2 cells submitted to oxidative stress. Importantly, supercritical fluid extract was more effective in inhibiting colorectal cancer cell growth (EC50 = 0.9 mg\/mL vs. 1.15 mg\/mL) than the hexane extract, and this effect was more pronounced than that obtained for pure \u03b3-oryzanol in the same concentration range. These findings highlight the potential of supercritical fluid technology to develop rice bran extracts with antioxidant and antiproliferative properties, underlining the promising applications of this technology in the field of natural product extraction.<\/jats:p>","DOI":"10.3390\/antiox14020206","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T11:54:06Z","timestamp":1739274846000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Optimization of Supercritical Fluid Extraction for the Recovery of \u03b3-Oryzanol-Rich Extracts with Improved Bioactivity from Rice Bran"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-7664","authenticated-orcid":false,"given":"Jo\u00e3o P.","family":"Baixinho","sequence":"first","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2450-1761","authenticated-orcid":false,"given":"Martim","family":"Cardeira","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-0586","authenticated-orcid":false,"given":"Andreia","family":"Bento-Silva","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, Av. das For\u00e7as Armadas, 1649-003 Lisboa, Portugal"}]},{"given":"Ana Maria Carvalho","family":"Partid\u00e1rio","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investiga\u00e7\u00e3o Agr\u00e1ria e Veterin\u00e1ria, I.P., Unidade de Tecnologia e Inova\u00e7\u00e3o, Av. da Rep\u00fablica, Quinta do Marqu\u00eas, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-8299","authenticated-orcid":false,"given":"Ana Teresa","family":"Serra","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Maria do Ros\u00e1rio","family":"Bronze","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"},{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia da Universidade de Lisboa, Av. das For\u00e7as Armadas, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-2966","authenticated-orcid":false,"given":"Naiara","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Saji, N., Francis, N., Schwarz, L.J., Blanchard, C.L., and Santhakumar, A.B. 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