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Hesperidin (HES), a phytoflavonoid glycoside found in citrus fruits such as oranges and lemons, has a variety of pharmacological effects. HES has been extensively studied to protect a variety of tissues from oxidative damage. However, it is not known whether HES may have a therapeutic effect on PCOS. In this study, potential therapeutic targets for HES treatment of PCOS were identified through network pharmacology, altered phosphorylation modification of JAK2 and PI3K was verified in granular cells of PCOS patients, and the mechanism of HES treatment of PCOS was revealed through in\u00a0vivo and in\u00a0vitro experiments. Based on network\u2010based pharmacological studies, PI3K\/Akt and JAK2\/STAT3 pathways are potential pathways for HES treatment of PCOS, and molecular docking results show that JAK2 has the best binding activity with HES. Western blotting results showed that the phosphorylation modification of JAK2 and PI3K in granular cells of PCOS patients was changed. Experiments in KGN cell lines have shown that HES can reduce DHT\u2010induced oxidative stress and apoptotic damage. Activating JAK2 or inhibiting PI3K can both reverse this therapeutic effect. In\u00a0vivo experiments have shown similar results. HES affects oxidative stress and apoptosis in PCOS through signaling crosstalk between JAK2\/STAT3 and PI3K\/AKT pathways.<\/jats:p>","DOI":"10.1002\/ptr.70100","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T12:05:09Z","timestamp":1758974709000},"page":"5174-5197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hesperidin Inhibits Oxidative Stress and Apoptosis of Granulosa Cells in Polycystic Ovarian Syndrome Through the\n                    <scp>JAK2<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    and\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7963-4672","authenticated-orcid":false,"given":"Qixuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Reproductive Medical Centre, Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Centre, Renmin Hospital of Wuhan University  Wuhan Hubei Province China"},{"name":"Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Reproduction and Development  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Ou","sequence":"additional","affiliation":[{"name":"Reproductive Medical Centre, Renmin Hospital of Wuhan University  Wuhan Hubei Province 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