Pharmacological Evaluation of Bergapten in High Fat Diet and Letrozole Induced Polycystic Ovarian Syndrome in Wistar Rats

Polycystic ovarian syndrome (PCOS) is a complex multifactorial endocrine and metabolic disorder associated with hormonal imbalance, insulin resistance and ovarian dysfunction. Moreover, obesity and dietary imbalance act as major contributing factors. The present study was designed to evaluate pharmacological effects of bergapten in a high-fat diet (HFD) and letrozole-induced PCOS models using Wistar rats. Animals were divided into different experimental groups and treated with bergapten at three doses (5, 10 and 20 mg/kg), with control groups maintained on HFD and letrozole. Body weight deviation, blood glucose levels, histopathological examination, serum biochemical analysis and gene expression profiling were used to determine therapeutic efficacy of bergapten. Results exhibited significant decrease in blood glucose and body weight in all bergapten treatment groups than diseased control. Serum analysis demonstrated normalization of hormonal (FSH, LH, estrogen, progesterone, testosterone,) and metabolic biomarkers (adiponectin, leptin, CYP19A1, CYP11A1, ALT, AST, ALP, cholesterol, total lipids, TGs, HDL). While gene expression studies through qRT-PCR showed significant downregulation of pro-inflammatory mediators such as TNF-α, IL-6, IL-8, Keap1 and upregulation of Nrf-2 pathway. In addition, partial recovery of PPAR-γ expression in bergapten treatment groups. The marked improvement in ovarian and hepatic tissues morphology further supported medicinal value of bergapten in attenuating metabolic stress. Overall, findings exhibited that bergapten not only alleviates PCOS but also counteracts obesity-related disturbances caused by HFD, suggesting its potential as a therapeutic candidate. Further investigations are needed to validate its clinical relevance.