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Grapefruit peel (\n GP<\/jats:styled-content>\n ), representing about 50% of the fruit's weight, is rich in sugars (soluble and insoluble) and polyphenols such as flavonoids. The present study investigates an integrated green extraction strategy using high\u2010intensity focused ultrasound (\n HIFU<\/jats:styled-content>\n ) and enzymatic hydrolysis (\n EH<\/jats:styled-content>\n ) to recover phenolic compounds and sugars from\n GP<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Vacuum\u2010drying preserved extractability and sugars release with the carbohydrases evaluated. Using dried\n GP<\/jats:styled-content>\n at 10% (\n DW<\/jats:styled-content>\n \/v),\n EH<\/jats:styled-content>\n incorporating lytic polysaccharide monooxygenases yielded >60\u2009g\u2009L\n \u20131<\/jats:sup>\n reducing sugars and 1\u20132.3\u2009g\u2009L\n \u20131<\/jats:sup>\n phenolics (gallic acid equivalents,\n GAE<\/jats:styled-content>\n ) after 24\u2009h. Optimal\n HIFU<\/jats:styled-content>\n conditions (46\u201357% amplitude, 40\u201359% ethanol v\/v, 11\u201332\u2009min) matched the phenolic yield of conventional extraction (20\u2009mg\n GAE<\/jats:styled-content>\n \u2009g\n \u20131<\/jats:sup>\n DW<\/jats:styled-content>\n ) but improved antioxidant capacity (53% 2,2\u2010diphenyl\u20101\u2010picrylhydrazyl inhibition\n vs.<\/jats:italic>\n 15%) at the same time as reducing solvent use (from 48 to 10\u201314.8\u2009\n mL<\/jats:styled-content>\n \u2009g\n \u20131<\/jats:sup>\n DW<\/jats:styled-content>\n ) and time (2\u2009h to 11\u201332\u2009min). Liquid chromatography\n \u2013tandem mass spectrometry<\/jats:styled-content>\n profiling identified key flavonoids and coumarins. Extracts exhibited selective cytotoxicity toward\n HeLa<\/jats:styled-content>\n and\n MCF7<\/jats:styled-content>\n cells and antimicrobial effects against\n Escherichia coli<\/jats:italic>\n at high concentrations. The solid residue from optimal\n HIFU<\/jats:styled-content>\n was subsequently subjected to\n EH<\/jats:styled-content>\n , yielding slightly less sugars and minimal phenolic compounds compared to the enzyme\u2010only process.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n Sequential\n HIFU<\/jats:styled-content>\n \u2010\n EH<\/jats:styled-content>\n offers an efficient, sustainable approach to valorize\n GP<\/jats:styled-content>\n , reducing solvent and time requirements at the same time as co\u2010producing bioactive phenolics and fermentable sugars in separate steps, thereby avoiding phenolic inhibition during subsequent biological steps. The process enhances antioxidant and antimicrobial properties and supports potential applications in food, nutraceutical and biorefinery sectors. \u00a9 2025 The Author(s).\n Journal of the Science of Food and Agriculture<\/jats:italic>\n published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jsfa.70312","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:50:42Z","timestamp":1764406242000},"page":"1839-1851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrated green extraction of phenolic compounds and fermentable sugars from grapefruit peel using ultrasound and enzymatic hydrolysis"],"prefix":"10.1002","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-6561","authenticated-orcid":false,"given":"Mar\u00eda del Prado","family":"Garc\u00eda\u2010Aparicio","sequence":"first","affiliation":[{"name":"Universidad de Alcal\u00e1, Departamento de Qu\u00edmica Anal\u00edtica Qu\u00edmica F\u00edsica e Ingenier\u00eda Qu\u00edmica, Campus Universitario Alcal\u00e1 de Henares Spain"},{"name":"Universidad de Alcal\u00e1, Instituto de Investigaci\u00f3n Qu\u00edmica \u2018Andr\u00e9s M. del R\u00edo\u2019 (IQAR), Campus Universitario Alcal\u00e1 de Henares Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-4103","authenticated-orcid":false,"given":"Mar\u00eda","family":"Castro\u2010Puyana","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Departamento de Qu\u00edmica Anal\u00edtica Qu\u00edmica F\u00edsica e Ingenier\u00eda Qu\u00edmica, Campus Universitario Alcal\u00e1 de Henares Spain"},{"name":"Universidad de Alcal\u00e1, Instituto de Investigaci\u00f3n Qu\u00edmica \u2018Andr\u00e9s M. del R\u00edo\u2019 (IQAR), Campus Universitario Alcal\u00e1 de Henares Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5583-1624","authenticated-orcid":false,"given":"Mar\u00eda Luisa","family":"Marina","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Departamento de Qu\u00edmica Anal\u00edtica Qu\u00edmica F\u00edsica e Ingenier\u00eda Qu\u00edmica, Campus Universitario Alcal\u00e1 de Henares Spain"},{"name":"Universidad de Alcal\u00e1, Instituto de Investigaci\u00f3n Qu\u00edmica \u2018Andr\u00e9s M. del R\u00edo\u2019 (IQAR), Campus Universitario Alcal\u00e1 de Henares Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wasman.2022.08.020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2gc36978h"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resconrec.2019.05.003"},{"key":"e_1_2_10_5_1","unstructured":"Food and Agriculture Organization of the United NationsGrapefruit production (including pomelos) 2023 data [FAOSTAT]. 2025. 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