Mechanism of Duonang NO.1 Alleviating Polycystic Ovary Syndrome by Modulating the Kiss1/Kiss1R/Akt/FoxO1 Signaling Pathway

OBJECTIVE To investigate the potential effect and mechanism of Duonang NO.1 (DNY) in treating polycystic ovary syndrome(PCOS) model rats.

METHODS Female SD rats were randomly divided into 6 groups: blank control group, model group, positive control group, DNY low-dose group, DNY medium-dose group, and DNY high-dose group, with 8 rats in each group. The PCOS rat model was established by continuous intragastric administration of letrozole for 21 days, and the body weight and estrous cycle of rats were observed to evaluate the modeling status. After successful modeling, the blank control and model groups were given normal saline by intragastric gavage, while the treatment groups received corresponding doses of drugs for 14 days. Body weight and ovarian weight were recorded, and the ovarian weight index was calculated. Hematoxylin-eosin staining was employed to observe ovarian histopathological changes. The levels of hormones including luteinizing hormone(LH) and follicle-stimulating hormone(FSH), as well as interleukin-6(IL-6), malondialdehyde(MDA), superoxide dismutase(SOD), and Kiss1 were measured by ELISA. RT-PCR was used to investigate the expression of FoxO1, CYP17A1, CYP19A1 mRNA in rats ovarian. The protein expression of Kiss1, P-Akt and FoxO1 were detected by immunohistochemistry(IHC). Western blotting was used to detect the protein expression of Kiss1, Kiss1R, Akt, P-Akt, and FoxO1 in ovarian tissue.

RESULTS Compared with the model group, DNY reduced the body weight growth rate, decreased serum levels of LH, LH/FSH ratio, T, AMH, IL-6, MDA, and Kiss1, and increased serum FSH, E₂, and SOD levels(P<0.05 or P<0.01). DNY improved ovarian pathological morphology. Compared with model group, the expression levels of FoxO1 and CYP17A1 mRNA were significantly decreased, the expression level of CYP19A1 mRNA was significantly increased(P<0.05 or P<0.01). Additionally, DNY downregulated the ovarian protein expression of Kiss1 and FoxO1, while upregulating the protein expression of Kiss1R and P-Akt/Akt(P<0.05 or P<0.01).

CONCLUSION DNY can improve sex hormone levels and alleviate ovarian pathological changes in PCOS rats. Its mechanism may be related to improving sex hormone secretion through the Kiss1/Kiss1R/Akt/FoxO1 signaling pathway.