Obacunone alleviated the development of polycystic ovary syndrome via inhibiting STAT3 phosphorylation

Obacunone (OB) possesses multiple pharmacological properties, including anti-inflammatory, anti-oxidant, anti-hyperglycemic, and anti-tumor activities. However, whether OB can ameliorate polycystic ovary syndrome (PCOS) remains unclear. This study aimed to investigate the influence and potential mechanism of OB on PCOS. PCOS mouse and cell models were established using dehydroepiandrosterone (DHEA). First, we evaluated the influence of OB on PCOS in mice by using hematoxylin and eosin staining of ovarian tissue, estrous cycle detection and biochemical analysis. Next, the functions of OB on apoptosis, oxidative stress, as well as inflammation in DHEA-treated KGN cells and DHEA-caused PCOS mice were further investigated utilizing western blot, quantitative real-time polymerase chain reaction, commercial test kits, flow cytometry and 2’,7’-dichlorodihydrofluorescein diacetate staining. Moreover, the potential mechanism of OB in PCOS was explored using network pharmacology, western blot, immunofluorescence and rescue experiments using Colivelin TFA, a signal transducer and activator of transcription 3 (STAT3) activator. OB treatment ameliorated ovarian function and corrected reproductive endocrine disorders in PCOS mice. Moreover, OB reduced apoptosis, oxidative stress as well as inflammation in both PCOS mouse and cell models, and inhibited STAT3 phosphorylation. Additionally, Colivelin TFA reversed the effects of OB on apoptosis, oxidative stress, and inflammatory responses in DHEA-treated KGN cells. Our findings demonstrated that OB alleviated the symptoms of PCOS via mitigating inflammation, apoptosis, and oxidative stress through the inhibition of STAT3 phosphorylation. OB improved ovarian function in PCOS mice. OB ameliorated reproductive endocrine disorder in PCOS mice. OB improved apoptosis, inflammatory responses and oxidative stress in PCOS. OB inhibited STAT3 phosphorylation in PCOS.