Disclosing Phytochemical Composition and Antifertility Potential of <i>Thevetia peruviana</i> (Pers.) K. Schum. Leaves

Overpopulation poses a global challenge, intensifying the need for safe and effective contraceptive agents. Thevetia peruviana (Pers.) K. Schum., traditionally used for various medicinal purposes, contains cardiac glycosides and other bioactive constituents with potential antifertility effects. This study investigated the phytochemical composition, reproductive toxicity, and spermicidal potential of T. peruviana leaf extract (TPLE) using RP-HPLC-MS/MS profiling and in vivo evaluation in male Wistar rats. Metabolomic analysis identified 52 compounds, including cardiac glycosides, flavonoids, hydroxycinnamic acids, and fatty acids. TPLE showed strong antioxidant activity and high phenolic/flavonoid content. Repeated administration (12-24 mg/kg for 60 days) caused a dose-dependent reduction in sperm motility and count, increased oxidative stress (↑MDA, ↓GSH), and dysregulated apoptotic/steroidogenic genes (↑casp-3, ↑bax, ↓bcl-2, ↓star, ↓cyp11a1). Histopathology revealed seminiferous tubule degeneration, Leydig cell necrosis, and caspase-3 overexpression. These results suggest that TPLE induces spermicidal effects through oxidative stress, apoptosis, and hormonal disruption, highlighting its potential as a plant-based contraceptive. However, toxicity at higher doses warrants further investigation into safety, reversibility, and translational potential.