Luteolin alleviates polycystic ovary syndrome in rats by resolving insulin resistance and oxidative stress

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by elevated secretion of androgen, commonly associated with insulin resistance (IR), which could exacerbate patient with PCOS. Development of a safe and effective treatment in preventing and treating PCOS will be beneficial to women of reproductive age. Female Sprague-Dawley rats were randomly divided into four groups: sham group treated with vehicle (saline) or luteolin; letrozole and high-fat-diet-induced PCOS group treated with vehicle or luteolin (25, 50, 100 mg/kg ip). Ovary tissue and blood were collected for further analysis. Luteolin normalized estrus cycle and improved ovarian morphology, including reduced polycystic and alleviated the loss of oocytes and corpus luteum in PCOS rats. Serum follicle stimulating hormone and estradiol were reduced, whereas luteinizing hormone and testosterone were elevated in PCOS rats relative to that of sham, which were significantly normalized by luteolin. Notably, luteolin significantly inhibited IR and upregulated protein levels of PI3K p85α and pAKT compared with PCOS rats treated with vehicle. In addition, the activities of antioxidants such as SOD, GPx, CAT, and GSH were reduced in PCOS rats, which were significantly increased by luteolin. Protein and mRNA expressions of Nrf2 and downstream genes such as Hmox1 and Nqo1 were restored by luteolin in PCOS rats. Collectively, this study demonstrated that luteolin inhibited IR by prompting PI3K/AKT signaling pathway and enhanced antioxidative response through the restoration of Nrf2 pathway.NEW & NOTEWORTHY Luteolin normalizes the estrus cycle, ovarian morphological changes, improves serum sexual hormone levels, reduces insulin resistance, prompts PI3K/Akt signaling, improves antioxidative response, and upregulates Nrf2 signaling in PCOS rats. Luteolin has a potential to serve as a therapeutic agent in preventing and treating PCOS.