Therapeutic mechanisms of metformin and Bushen Ditan Decoction in polycystic ovary syndrome: Evidence from a rat model and miRNA sequencing

Background: Polycystic ovary syndrome (PCOS) represents the most common endocrine disorder afflicting women of reproductive age. PCOS is characterized by hormonal imbalances, metabolic abnormalities, and infertility, yet only limited therapeutic options are available. Metformin and Bushen Ditan Decoction (BDD), a traditional Chinese medicine formula, are commonly used in Western and traditional Chinese medicine, respectively, for treating PCOS. Despite their demonstrated clinical efficacy, the mechanisms underlying their therapeutic effects remain incompletely understood. Objective: This study aimed to investigate the therapeutic mechanisms of metformin and BDD in a PCOS rat model. Methods: PCOS was induced in rats by using the Poretsky method. After model induction, the animals were given metformin (150 mg/kg/day) or BDD (8, 16, or 32 mg/kg/day) via intragastric gavage for 4 weeks. Results: Both metformin and BDD significantly reduced testosterone levels and improved lipid metabolism parameters. MicroRNA (miRNA) sequencing of ovarian tissues identified 18 miRNAs commonly regulated by both treatments, and functional enrichment analysis indicated that these differentially expressed miRNAs are involved in autophagy- and metabolism-related pathways implicated in the pathogenesis of PCOS. Conservation analysis across species highlighted the potential clinical relevance of these findings. Conclusion: This study demonstrated how mechanistically metformin and BDD work on PCOS, particularly through the regulation of autophagy- and metabolism-related pathways, providing insights for their future clinical applications.