Laurolitsine ameliorates insulin resistance, ovarian dysfunction and gut microbiota dysbiosis in DHEA plus HFD-induced PCOS mice

Background Polycystic ovary syndrome (PCOS) is a complex endocrine reproductive disorder that affects 10%-13% of women worldwide, characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovary formation. Currently, there are no effective specific treatments for PCOS. Therefore, identifying safe and effective therapeutic drugs for PCOS is clinically important. Methods In this study, a PCOS mouse model was induced using dehydroepiandrosterone (DHEA) plus high-fat diet (HFD) to investigate the therapeutic effects of laurolitsine (LL). The efficacy of LL was evaluated by estrous cycle, glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum biochemical markers. Histopathological analysis of ovarian, gonadal fat, and liver tissues was performed using hematoxylin and eosin (H&E) staining. Furthermore, RNA-seq analysis and 16S rRNA sequencing were performed to explore the potential mechanisms underlying LL’s effects on PCOS mice. Results LL exhibited therapeutic effects in PCOS mice. LL improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, and ovarian dysfunction in PCOS mice. RNA-seq analysis revealed that LL may improve PCOS by modulating key metabolic processes, including hormone response, fatty acid metabolism, and lipid metabolism in the ovaries. Additionally, LL significantly modulated the gut microbiota composition in PCOS mice, particularly reducing the abundance of Proteobacteria and Lactobacillus johnsonii , while increasing the abundance of Akkermansia muciniphila . Conclusion LL is a promising and novel therapeutic agent for PCOS, as it ameliorates insulin resistance, ovarian dysfunction, and gut microbiota.