Box-Behnken experimental design for a green extraction method of phenolic compounds from olive leaves Martín García, Beatriz Pimentel Moral, Sandra Gómez Caravaca, Ana María Arráez Román, David Segura Carretero, Antonio Pressurized liquid extraction Phenolic compounds HPLC-ESITOF-MS Olive leaves Box-Behnken design Response surfaces This study was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (project AGL2015-67995-C3-2), by the Ministry of Science, Innovation and UniversitiesRTI2018-096724-B-C22 and by the Ministry of Economy, Knowledge and Business and the University of the Junta de AndalucíaB-AGR-466-UGR18. The authors are also grateful to the University of Granada for a “Contrato Puente” postdoctoral contract. Olive leaves are important olive by-products due to their high content of phenolic compounds and elenolic acids, which possess antioxidant, antimicrobial, anti‐atherogenic and anti‐inflammatory properties, among others. Thus, pressurized liquid extraction was used to obtain a high recovery of these compounds from olive leaves. A Box-Behnken design was performed to optimize the PLE conditions of temperature (50−200 °C), % ethanolwater (0–100 %) and extraction time (5−20 min) in order to obtain the highest content of simple phenols, secoiridois, flavonoids, elenolic acids, total compounds and extraction yield from olive leaves. Olive leaf extracts were analyzed by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The highest content of total compounds was 158.7 ± 0.4 mg g-1 d.w obtained at 105 °C, 100 % ethanol and 5 min, whereas the highest extraction yield was 43 ± 3% obtained at 198 °C, 100 % ethanol and 5 min. Therefore, multi-response analysis was carried out using desirability function to optimize the PLE conditions for both total compounds and yield. These optimal conditions were 138 °C, 100 % EtOH and 5 min obtaining 144 mg g-1 d.w. of total compounds and 42.2 % of yield. The optimal temperature of 138 °C has shown a great phenolic recovery and 100 % ethanol has been shown to be a safe solvent to use in the food industry. In addition, short extraction times (5 min) mean lower energy consumption and lower costs. Therefore, these PLE optimum conditions could be implemented on an industrial scale. 2025-03-27T11:46:16Z 2025-03-27T11:46:16Z 2020-06-29 journal article Published version: Martín García, Beatriz et al. Industrial Crops & Products 2020, 154 (112741). https://doi.org/10.1016/j.indcrop.2020.112741 https://hdl.handle.net/10481/103306 10.1016/j.indcrop.2020.112741 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier