{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:09:38Z","timestamp":1773677378467,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University","award":["IMSIU-DDRSP2602"],"award-info":[{"award-number":["IMSIU-DDRSP2602"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The valorization of agro-industrial by-products is a sustainable approach to recovering high-value bioactive compounds. In this study, Opuntia ficus-indica (L.) Mill. seed press residues were investigated as a source of phenolic and flavonoid compounds using microwave-assisted extraction (MAE). A multi-step optimization strategy was implemented, combining preliminary single-factor experiments (OVAT), response surface methodology based on a Box\u2013Behnken design (BBD), and machine learning modeling using K-nearest neighbors coupled with the dragonfly algorithm (KNN_DA), followed by desirability-based validation. The effects of ethanol concentration (50\u2013100%), microwave power (400\u2013800 W), extraction time (2\u20134 min), and liquid-to-solid ratio (30\u201350 mL\/g) were evaluated on Folin\u2013Ciocalteu reducing capacity (FCRC), AlCl3 complexation response, and antioxidant activity assessed by DPPH radical scavenging and reducing power assays. Optimal conditions were identified at 50% ethanol, 800 W microwave power, 4 min extraction time, and a liquid-to-solid ratio of 47.28 mL\/g. Under these conditions, FCRC reached 376.85 \u00b1 0.23 mg GAE\/100 g DW and 49.16 \u00b1 0.33 mg QE\/100 g DW for AlCl3 complexation response, with prediction errors of 2.80% and 0.82%, respectively. The optimized extracts exhibited enhanced antioxidant activity. These findings confirm MAE as a rapid and environmentally friendly technique and highlight the predictive performance of the KNN_DA model for process optimization.<\/jats:p>","DOI":"10.3390\/molecules31060998","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:30:32Z","timestamp":1773671432000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Machine Learning and Microwave-Assisted Green Extraction: Total Colorimetric Response Assay-Based Optimization of Opuntia ficus-indica Seed Residues"],"prefix":"10.3390","volume":"31","author":[{"given":"Souad","family":"Khaled","sequence":"first","affiliation":[{"name":"Centre de Recherche en Technologies Agro-Alimentaires, Route de Targa Ouzemmour, Campus Universitaire, Bejaia 06000, 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