Ameliorative Effect of Chitosan-Propolis Nanoparticles on the Estradiol Valerate-Induced Polycystic Ovary Syndrome Model

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women. Previous research has shown that PCOS is associated with insulin resistance, oxidative stress, and immune system malfunctions. Also, the antioxidant effects of propolis and the positive effects of chitosan nanoparticles on the reproductive system have been demonstrated in some reports. Objectives: The current study is designed to investigate the protective effects of chitosan-propolis nanoparticle against estradiol valerate-induced (EV) PCOS model of rats compared to metformin (Met) (as a control treatment). Methods: Intramuscular injection of EV (4 mg/kg, 28 days) was used to induce PCOS in rats, followed by oral administration of 500 mg/kg chitosan-propolis nanoparticle for 42 days. Rats were divided into 4 groups: Control, PCOS, metformin (PCOS and 150 mg/kg metformin), and chitosan-propolis nanoparticles (PCOS and chitosan-propolis nanoparticle administration, 500 mg/kg) groups. Results: All animals were subjected to serum factors analysis and histopathological study of ovaries. Estradiol valerate-induced induced PCOS while administration of chitosan-propolis nanoparticle recovered it. The body weight (P < 0.01) and ovarian morphology improved. The serum biochemical parameters, including estrogen (P < 0.05), progesterone (P < 0.001), vitamin D (P < 0.01), calcium (P < 0.01), and insulin resistance index (P < 0.05) were reversed after chitosan-propolis nanoparticle intervention. These EV-induced alterations included inhibited superoxide dismutase (SOD) activity (P < 0.05) and increased malondialdehyde (MDA) level (P < 0.001), and it was demonstrated that chitosan-propolis nanoparticle/Met administered for 42 consecutive days and gavages with EV reversed the oxidative stress factors. Additionally, in EV-treated animals, there was a significant upregulation of certain relative mRNA expressions, such as monocyte chemoattractant protein (MCP) (P < 0.01), interleukin 18 (IL-18) (P < 0.05), and C-reactive protein (CRP) (P < 0.01) genes. These data clearly show that chitosan-propolis nanoparticle/Met may have a protective effect on this inflammatory disorder. Conclusions: Taken together, the final results of this study are consistent with the assumption that chitosan-propolis nanoparticle /Met had ameliorative and protective effects against the harmful effects of EV. Although it is hypothesized that ameliorative effects might have been involved, the fundamental pathways remain to be illuminated.