Bushen Huatan formula alleviates polycystic ovary syndrome in rats by activating the PI3K/Akt pathway to inhibit GSDMD-mediated pyroptosis and mitochondrial damage
Abstract
BACKGROUND: Previous studies suggest that the traditional Chinese medicinal formula Bushen Huatan Fang (BSHT) possesses the capacity to modulate hormonal levels in patients with endocrine and metabolic disorders, indicating its potential clinical utility. This study aims to elucidate the specific mechanisms through which BSHT exerts therapeutic effects in a rat model of polycystic ovary syndrome (PCOS).
METHODS: A PCOS model was established in female Sprague-Dawley rats using a high-fat diet and letrozole. Rats were randomly assigned to control, model, positive control (metformin), and BSHT low dose (BSHT-L), medium dose (BSHT-M), and high dose (BSHT-H) groups, with interventions administered for 31 days. Endocrine markers (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), insulin resistance (fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR)), and ovarian function were assessed by enzyme-linked immunosorbent assay (ELISA), histopathology, and immunohistochemistry. Inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), lactate dehydrogenase (LDH), mitochondrial function (reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATPase activity), and pyroptosis markers (generating its GSDMD-N, cleaved caspase-1, IL-1β) were measured by Western blot. Network pharmacology predicted BSHT's…
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