Hesperidin Inhibits Oxidative Stress and Apoptosis of Granulosa Cells in Polycystic Ovarian Syndrome Through the <scp>JAK2</scp> / <scp>STAT3</scp> and <scp>PI3K</scp> / <scp>AKT</scp> Pathways

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder syndrome in women of childbearing age. 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 vivo and in vitro experiments. Based on network-based 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-induced oxidative stress and apoptotic damage. Activating JAK2 or inhibiting PI3K can both reverse this therapeutic effect. In vivo experiments have shown similar results. HES affects oxidative stress and apoptosis in PCOS through signaling crosstalk between JAK2/STAT3 and PI3K/AKT pathways.