{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:03:55Z","timestamp":1789383835913,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan Fundamental Research Projects","award":["202501AT070150"],"award-info":[{"award-number":["202501AT070150"]}]},{"name":"Yunnan Fundamental Research Projects","award":["202401AT070216"],"award-info":[{"award-number":["202401AT070216"]}]},{"name":"Yunnan Province-City Integration Project","award":["202505AV340010"],"award-info":[{"award-number":["202505AV340010"]}]},{"DOI":"10.13039\/501100007846","name":"Yunnan Provincial Department of Education","doi-asserted-by":"publisher","award":["2024J0512"],"award-info":[{"award-number":["2024J0512"]}],"id":[{"id":"10.13039\/501100007846","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024J0512"],"award-info":[{"award-number":["2024J0512"]}],"id":[{"id":"https:\/\/ror.org\/02yrxdp92","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The rising global prevalence of hyperuricemia has intensified the search for natural xanthine oxidase (XO) inhibitors from food-grade botanicals. This study screened leaf extracts from four plant species for XO inhibitory activity and identified raspberry leaf as the most potent source. Among seven extraction and pre-treatment methods, ultrasound-assisted extraction (UAE) outperformed conventional decoction and all alternatives. Box\u2013-Behnken response surface methodology optimized UAE parameters to 70 \u00b0C, 50 min, and a solid-to-liquid ratio of 1:20 g\/mL, yielding an extract with 97.77 \u00b1 0.08% XO inhibition and an IC50 of 0.3433 mg\/mL\u2014a 5.34-fold potency gain over decoction. Kinetic characterization established a reversible mixed-type inhibition mechanism (Ki = 0.147 mg\/mL), alongside parallel improvements in DPPH, ABTS, and hydroxyl radical scavenging. Widely targeted UHPLC-MS\/MS metabolomics identified 2987 metabolites; network pharmacology and molecular docking revealed that the origin of XO inhibition potentially involves terpenoids and coumarins\u2014not the flavonoid and polyphenol fractions conventionally assumed\u2014with dihydroactinidiolide, 7-hydroxy-8-methoxycoumarin, and piperlongumine as the candidate active constituents. These results position UAE-optimized raspberry leaf extract as a promising natural functional ingredient for hyperuricemia management and expand the phytochemical scope of plant-derived XO antagonists beyond flavonoids.<\/jats:p>","DOI":"10.3390\/foods15183231","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:34:01Z","timestamp":1789378441000},"page":"3231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Metabolomics and Network Pharmacology to Identify Xanthine Oxidase Inhibitors from Raspberry Leaf: Optimization by Ultrasound-Assisted Extraction and Kinetic Characterization"],"prefix":"10.3390","volume":"15","author":[{"given":"Zuoming","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, 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