{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:03:38Z","timestamp":1790820218485,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Modified Huanglian Wendan Decoction (HLWDD) is used for polycystic ovary syndrome with insulin resistance (PCOS\u2010IR), but its biological basis remains incompletely defined. This study integrated network pharmacology, molecular docking, 100\u2010ns molecular dynamics (MD), batch\u2010specific chemical characterization, and in vivo evaluation in a letrozole\/high\u2010fat diet rat model. HPLC fingerprinting showed high batch reproducibility, while UHPLC\u2013HRMS\/MS identified 997 candidate library assignments, including 118 higher\u2010confidence features. Network analysis identified 136 candidate compounds and 532 overlapping PCOS\u2010related targets, prioritizing AGE\u2013RAGE signaling. Representative docked complexes remained stable during MD and showed negative MM\/PBSA binding free energies. In vivo, HLWDD improved estrous\u2010cycle recovery and ovarian morphology, reduced fasting insulin, HOMA\u2010IR, reproductive hormones, and inflammatory markers, and modulated ovarian AGE, RAGE, STAT3, and AKT1 expression. High\u2010dose HLWDD also reduced p\u2010STAT3\/STAT3 and increased p\u2010AKT\/AKT1 relative to the Model group. These findings support an association between HLWDD treatment and AGE\u2013RAGE\/STAT3\/AKT\u2010related signaling without establishing causal pathway mediation.<\/jats:p>","DOI":"10.1002\/cbdv.71737","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:39:51Z","timestamp":1790818791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology and In Vivo Evaluation of Modified Huanglian Wendan Decoction in Polycystic Ovary Syndrome With Insulin Resistance: Association With AGE\u2013RAGE\u2010Related Signaling"],"prefix":"10.1002","volume":"23","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine Hubei University of Chinese Medicine  Wuhan China"},{"name":"Department of Gynecology Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"},{"name":"Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinni","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Gynecology Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9713-4263","authenticated-orcid":false,"given":"Chenghong","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Hubei University of Chinese Medicine  Wuhan China"},{"name":"Wuhan Hospital of Traditional Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"36","key":"e_1_2_14_2_1","first-page":"3812","article-title":"Polycystic Ovary Syndrome: A Contemporary Clinical Approach","volume":"27","author":"Bjeki\u0107\u2010Macut J.","year":"2021","journal-title":"Current Pharmaceutical Design"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.963213","article-title":"Mapping Research Trends of Insulin Resistance in Polycystic Ovary Syndrome From 2017 to 2021: A Bibliometric Analysis","volume":"13","author":"Chen Y.","year":"2022","journal-title":"Frontiers in Endocrinology"},{"issue":"1","key":"e_1_2_14_4_1","doi-asserted-by":"crossref","DOI":"10.15190\/d.2022.4","article-title":"Novel Antidiabetic Medications in Polycystic Ovary Syndrome","volume":"10","author":"Somagutta M. 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