Effects of Total Flavonoids From Rubus chingii Hu on the Hypothalamic-Pituitary-Ovarian Axis and Inflammatory...

Polycystic ovary syndrome (PCOS) is a common reproductive disorder in women of childbearing age, posing serious risks to both physical and mental health. Dysregulation of the hypothalamic-pituitary-ovarian (HPO) axis and inflammatory responses are key pathological mechanisms, yet there are currently no specific therapeutic drugs available. Therefore, this study investigates the ameliorative effects of total flavonoids from Rubus chingii Hu (RHF) on HPO axis function and inflammatory response in a rat model of PCOS induced by letrozole. The results demonstrated that RHF restored the disrupted estrous cycle in PCOS rats. It significantly reduced ovarian weight, index, length, width, area, and volume. Moreover, RHF treatment decreased the ovarian mRNA levels of BCL-2-associated X protein (Bax) and aspartate specific cysteine protease (Caspase)-3 while increasing that of B-cell lymphoma-2 (Bcl-2), collectively ameliorating ovarian pathological changes. Concurrently, RHF significantly lowered serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and testosterone (T), while elevating follicle-stimulating hormone (FSH), estradiol (E₂), and sex hormone-binding globulin (SHBG), indicating its potential to mitigate hypothalamic-pituitary-ovarian (HPO) axis dysfunction. Furthermore, RHF reduced peripheral blood counts of white blood cells (WBC), platelets (PLT), red blood cell distribution width (RDW), the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, as well as serum interleukin-18 (IL-18), IL-1β, tumor necrosis factor-α (TNF-α), and IL-6. In ovarian tissue, RHF downregulated the protein and mRNA expression of NLRP3, caspase-1, the N-terminal fragment of gasdermin D (GSDMD-NT), IL-18, and IL-1β, and lowered the mRNA levels of IL-6 and TNF-α, thereby attenuating both systemic and local ovarian inflammatory responses. Taken together, these findings demonstrate that RHF confers protective effects in PCOS rats, which are associated with the amelioration of HPO axis function and suppression of inflammatory responses.