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Despite its high prevalence, specific pharmacological interventions for PCOS remain limited. GeGen Decoction (GGD), documented since the Han Dynasty, has been continuously explored for its modern applications. Currently, it is frequently utilized to treat gynecological and metabolic disorders, including PCOS. Our study applied in\u00a0vivo models utilizing dehydroepiandrosterone (DHEA)\u2010induced PCOS rats and in\u00a0vitro models employing dihydrotestosterone (DHT) combined with palmitic acid (PA) and oleic acid (OA) to induce KGN cells, to confirm the effects of GGD on PCOS and to explore the mechanism of action. Our findings demonstrated that GGD effectively alleviated PCOS symptoms in rat models by improving estrous cycles, restoring ovarian morphology, regulating hormone levels, and ameliorating glucose and lipid metabolism disorders. Mechanistically, GGD maintained cholesterol homeostasis by modulating the interaction between sterol O\u2010acyltransferase 2 (ACAT2) and insulin\u2010induced gene 1 (INSIG1), thereby enhancing the intracellular environment of KGN cells, promoting the expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and subsequently mitigating PCOS\u2010related symptoms. Our data indicate that GGD may serve as a potential therapeutic agent for PCOS.<\/jats:p>","DOI":"10.1096\/fj.202500192rr","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T11:51:32Z","timestamp":1751025092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Potential of\n                    <scp>GeGen<\/scp>\n                    Decoction for the Treatment of Polycystic Ovary Syndrome"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6738-3716","authenticated-orcid":false,"given":"Yiwen","family":"Qian","sequence":"first","affiliation":[{"name":"Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, School of Traditional Pharmacy China Pharmaceutical University  Nanjing 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