{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:49:07Z","timestamp":1791013747075,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan"},{"name":"Europe-an Union\u2014NextGenerationEU","award":["CN_00000033"],"award-info":[{"award-number":["CN_00000033"]}]},{"name":"Italian Ministry of University and Research","award":["D43C22001260001"],"award-info":[{"award-number":["D43C22001260001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Within the framework of green chemistry and wild fruit valorization, this study optimizes the extraction of bioactive compounds from Prunus spinosa L. fruits using glycerin-based ultrasound-assisted extraction (UAE). Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) were comparatively employed to model the process. Significant improvements in extraction efficiency were achieved, with total phenolic content increasing from 9.28 to 23.22 mg GAE\/g DW, total flavonoid content from 6.53 to 21.65 mg CE\/g DW, and antioxidant activity (DPPH assay) from 57.04% to 86.34%. While both models performed well, ANN demonstrated slightly higher predictive accuracy, highlighting its potential for capturing complex, non-linear relationships in the extraction process. We identified the optimal extraction conditions as 9 min extraction time, 100% ultrasonic amplitude, and 40% water in glycerin, and these conditions were experimentally validated. UHPLC-DAD-HRMS\/MS profiling revealed a rich phytochemical fingerprint dominated by phenolic acids, caffeoylquinic acid derivatives, and flavonol glycosides, and revealed largely overlapping qualitative phytochemical profiles between hydroglyceric and ethanolic extracts. Comparative extraction using 70% ethanol under identical conditions resulted in lower TPC, TFC, and antioxidant activity, indicating the improved efficiency of glycerin under the investigated conditions. Overall, the optimized glycerin-based UAE provides a sustainable, food-safe approach for extracting bioactive compounds from underutilized P. spinosa fruits. These results support its application in functional foods and in nutraceutical and cosmetic formulations.<\/jats:p>","DOI":"10.3390\/antiox15020202","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:03:29Z","timestamp":1770113009000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optimization of Bioactive Compound Extraction from Prunus spinosa L. Fruits Using Ultrasound-Assisted Extraction with Food-Grade Glycerin: A Combined RSM\u2013ANN Approach"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4413-3303","authenticated-orcid":false,"given":"Asmaa","family":"Berkati","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Bejaia, Facult\u00e9 des Sciences de la Nature Et de la Vie, Laboratoire de Biomath\u00e9matique, Biochimie, Biophysique et Scientom\u00e9trie (L3BS), Bejaia 06000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Ben Hamiche","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bejaia, Facult\u00e9 des Sciences de la Nature Et de la Vie, Laboratoire de Biomath\u00e9matique, Biochimie, Biophysique et Scientom\u00e9trie (L3BS), Bejaia 06000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-3382","authenticated-orcid":false,"given":"Amina","family":"Kribeche","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bejaia, Facult\u00e9 des Sciences de la Nature Et de la Vie, Laboratoire de Biomath\u00e9matique, Biochimie, Biophysique et Scientom\u00e9trie (L3BS), Bejaia 06000, Algeria"},{"name":"Department of Food Sciences, University of Mouloud Mammeri, Tizi-Ouzou 15000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louiza","family":"Himed","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology and Food Quality (BIOCQUAL), Institute of Nutrition, Food and Agri-Food Technologies (INATAA), University of Constantine 1, Constantine 25000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2037-0485","authenticated-orcid":false,"given":"Salah","family":"Merniz","sequence":"additional","affiliation":[{"name":"Institute of Industrial Hygiene and Safety, University Batna 2, Batna 05000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5315-3055","authenticated-orcid":false,"given":"Maria","family":"D\u2019Elia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"},{"name":"Dipartimento di Scienze della Terra e del Mare, University of Palermo, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-594X","authenticated-orcid":false,"given":"Rita","family":"Celano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-5450","authenticated-orcid":false,"given":"Luca","family":"Rastrelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1021\/np50082a008","article-title":"Constituents of Prunus spinosa","volume":"55","author":"Irizar","year":"1992","journal-title":"J. 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