Cinnamaldehyde mitigates polycystic ovary syndrome pathologies by modulating NLRP3/NF-κB mediated inflammation using letrozole-induced model in female rats: a comprehensive in vitro,in vivo, in silico investigation.

Abstract

Polycystic ovary syndrome (PCOS) is a complicated endocrine disease marked by hyperandrogenism, inflammation, hyperglycemia, and disrupted ovulation. This research examined the therapeutic effect of cinnamaldehyde in alleviating PCOS-associated complications in rats administered with letrozole. Letrozole-induced PCOS rats exhibit symptoms similar to human PCOS, including hormonal imbalance, insulin resistance, and dyslipidemia. This study identified NF-κB and NLRP3 as key target genes of cinnamaldehyde's anti-inflammatory effects in the context of PCOS. Molecular docking analysis suggested that cinnamaldehyde modulates the activity of these genes, which play critical roles in the inflammatory response. PCOS was induced in female Sprague-Dawley rats using letrozole (1 mg/kg) for 6 weeks. Cinnamaldehyde treatment (5, 10, and 20 mg/kg/day) for 21 days resulted in a significant reduction in body weight, luteinizing hormone levels, serum testosterone concentration, ovarian cysts formation, lipid profile markers, and glycemic parameters. Cinnamaldehyde also exhibited anti-inflammatory effects by negatively regulating NLRP3, caspase-1, NF-κB mRNA expression, IL-18 and IL-1β. Additionally, cinnamaldehyde showed antioxidant effects by elevating SOD and GSH levels and exhibited potential effects in ABTS and DPPH assays. These mechanisms likely contributed to the observed improvements in hormonal balance, ovarian function, and metabolic profile. Overall, this study highlights the potential therapeutic value of cinnamaldehyde in managing PCOS-associated complications, particularly through its anti-inflammatory and antioxidant effects, and suggests its potential as a novel treatment strategy for this complex endocrine disorder.