{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:21:10Z","timestamp":1787822470111,"version":"build-2784847793"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH306"],"award-info":[{"award-number":["ZR2022MH306"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2026MS1381"],"award-info":[{"award-number":["ZR2026MS1381"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hyperuricemia (HUA) is a common metabolic disorder with limited safe and effective therapeutic options. This study integrated GEO dataset mining and network pharmacology to explore the anti\u2010HUA efficacy and mechanism of pomegranate peel polyphenol extract (PPE). In a mouse model of HUA induced by potassium oxonate and 5% fructose water, PPE significantly reduced serum, urinary, and fecal uric acid levels, attenuated the increases in creatinine and blood urea nitrogen, improved estimated glomerular filtration rate, and ameliorated renal pathological damage, inflammation, and xanthine oxidase activity. Integration of GEO\u2010derived HUA\u2010related genes and computational target prediction for PPE identified 44 common targets, and protein\u2013protein interaction network analysis revealed core targets including Akt1. KEGG enrichment highlighted the PI3K\u2010AKT signaling pathway as a key mediator. Western blotting in\u00a0vivo and in\u00a0vitro confirmed that PPE suppressed PI3K\u2010AKT phosphorylation and downregulated the urate reabsorption transporters URAT1 and GLUT9. Furthermore, experiments in UA\u2010induced HK\u20102 cells demonstrated that ellagic acid, a major bioactive component of PPE, acted through the same pathway. These findings indicate that PPE reduces uric acid levels and protects the kidney via modulation of the PI3K\u2010AKT pathway, providing an integrative data\u2010driven rationale for its potential as a functional food or pharmaceutical agent against HUA.<\/jats:p>","DOI":"10.1111\/cbdd.70376","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:36:54Z","timestamp":1786001814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pomegranate Peel Polyphenol Extract Ameliorates Hyperuricemia by Inhibiting Uric Acid Synthesis and Reabsorption"],"prefix":"10.1111","volume":"108","author":[{"given":"Zeyu","family":"Yin","sequence":"first","affiliation":[{"name":"School of Life Sciences and Medicine Shandong University of Technology  Zibo Shandong People's Republic of 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