Escin ameliorates letrozole-induced polycystic ovarian syndrome by modulating inflammatory, oxidative stress, and steroidogenic pathways in Wistar rats: integration of network pharmacology and molecular docking
Abstract
Polycystic ovary syndrome (PCOS) is a multifarious and chronic hormonal disease of women that is marked by hyperandrogenism, insulin resistance, and continued anovulation. This study aimed to evaluate the therapeutic effect of escin in PCOS. For this purpose, a network pharmacology and molecular docking study was performed to find potential targets and to explore the interaction of escin with major proteins associated with PCOS pathogenesis, including CYP19A1, the estrogen receptor, TNF-α, and SHBG. In this study, letrozole (1 mg/kg) was administered orally for 28 days to induce PCOS in all Wistar rats except for normal control. After PCOS induction, normal and PCOS + Veh group received 1 ml of 0.5% CMC, PCOS + Met treated with metformin (300 mg/kg), whereas treatment groups received PCOS + Escin 5, 10, and 15 mg/kg daily via oral route for 28 days. At the end of the experiment, body weight, oral glucose, hormonal level (sex hormone-binding globulin (SHBG), estrogen, progesterone, luteinizing hormone, follicle-stimulating hormone (FSH), testosterone), lipid profile, and liver tests were performed. Activity of CAT and SOD, and level of MDA and reduced GSH were measured in the ovary homogeneity. mRNA expression of TNF-α, IL-6, Nrf2/Keap-1, PGR, FSHR, and CYP19A1 were quantified in ovarian tissue by real-time PCR. The docking analysis demonstrated favorable binding affinities and stable ligand-protein interactions to CYP19A1, estrogen receptor, TNF-α, and SHBG, suggesting that…
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