Ameliorative character of eugenol and propargylated eugenol against letrozole induced polycystic ovarian syndrome in in-vivo zebrafish model.

Polycystic ovary syndrome (PCOS) is an endocrine condition that mainly affects female reproductive function and is often linked with metabolic disturbances. Letrozole (LET), though widely used for ovulation induction, may induce PCOS-like conditions with prolonged exposure. In this study, we evaluated the protective effect of eugenol (EU) and its derivative propargylated eugenol (PEU) against letrozole-induced PCOS using an in vivo zebrafish model. Molecular docking helped, that both compounds interact with key PCOS-related targets, with PEU exhibiting relatively stronger binding affinity. In vivo exposure to letrozole resulted in reduced sexual behaviour, decreased fecundity, elevated glucose levels, increased oxidative stress and delayed ovarian development. Treatment with eugenol and propargylated eugenol has improved mating behavior, restored spawning ability, normalized gonadosomatic index (GSI) and reduced fasting blood glucose levels. Antioxidant assays revealed decreased lipid peroxidation, improved SOD and CAT activity in treated groups. Furthermore, the analysis of ovarian tissue sections corroborated the resumption of ovarian follicular development and a decrease in collagen deposition validated including Masson's trichrome (MTS), Picrosirius red (PSR). Gene expression investigations demonstrated the reinstatement of steroidogenic markers such as cyp19a1a, alongside inflammatory marker. These observations suggest that the synthesized compounds exert considerable effects, with propargylated eugenol exhibiting numerically greater efficacy across most assays. Consequently, these results imply that eugenol derivatives could function as potential adjunctive agents in the management of letrozoles-induced PCOS, specifically by addressing oxidative stress, hormonal imbalances, and ovarian dysfunction.