{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:52:40Z","timestamp":1780055560371,"version":"3.54.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    This study investigated the therapeutic effects and mechanisms of\n                    <jats:italic>Paeonia suffruticosa<\/jats:italic>\n                    fruit pod extract (EMP) and its main component albiflorin (AF) on hyperuricemia\u2010associated cognitive impairment (HUA\u2010CI). A HUA\u2010CI mouse model was established, with cognitive function evaluated via Morris water maze. Hippocampal pathology, inflammation, oxidative stress, and apoptosis were assessed using HE staining, ELISA, TUNEL, and Western blotting. Network pharmacology predicted EMP\u2019s targets, and molecular docking analyzed AF\u2010MAP2K1 binding. In vitro experiments used UA\u2010stimulated BV2 and HT22 cells to explore AF\u2019s effect on HIF\u20101 signaling. EMP significantly improved cognitive function and reduced pathological damage in the hippocampus of HUA\u2010CI mice. It exerted protective effects by inhibiting inflammatory responses, alleviating oxidative stress, and preventing cell apoptosis. Network pharmacology analysis revealed that EMP acts through multiple targets and pathways, particularly via the strong binding affinity between AF and MAP2K1. Both in vivo and in vitro studies demonstrated that AF inhibited the HIF\u20101 signaling pathway, thereby reducing microglial activation and associated inflammation, mitigating uric acid\u2010induced neuronal apoptosis, enhancing antioxidant defenses, and protecting neuronal function. Our research indicates that EMP exerts multi\u2010target therapeutic effects on HUA\u2010CI; AF plays a key role by targeting MAP2K1 and inhibiting HIF\u20101 signaling.\n                  <\/jats:p>","DOI":"10.1155\/humu\/5859468","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:47:26Z","timestamp":1768823246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Albiflorin\u2010Mediated MAP2K1 Targeting and HIF\u20101 Signaling Inhibition Contribute to the Therapeutic Efficacy in Hyperuricemia\u2010Associated Cognitive Impairment"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-1489","authenticated-orcid":false,"given":"Huimin","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-7633","authenticated-orcid":false,"given":"Jincai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5579-7278","authenticated-orcid":false,"given":"Linrui","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1314-8855","authenticated-orcid":false,"given":"Jinming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11082212"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.S232377"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/npr2.12445"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2022.08.129"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.15420\/ecr.2015.10.01.60"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu10080975"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03302-5"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-018-1136-y"},{"key":"e_1_2_8_9_2","first-page":"775","article-title":"The Role of Hyperuricemia in the Development of Cognitive Changes in the Elderly","volume":"35","author":"Kunitskaya N. 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