Protective Effects of <i>Ephedra pachyclada</i> Boiss. Extract Against Pyriproxyfen‐Induced Male Reproductive Toxicity: Modulation of Oxidative and Inflammatory Pathways

Excessive pesticide exposure is increasingly associated with oxidative stress mediated reproductive toxicity. Pyriproxyfen (PPF), a widely used juvenile hormone analog insecticide, has been implicated in oxidative stress mediated reproductive toxicity. This study investigated the mechanisms underlying PPF-induced testicular damage and evaluated the protective potential of Ephedra pachyclada extract (EPE), focusing on modulation of the Nrf2/ARE and NF-κB pathways. Adult male rats were exposed to PPF (20 mg/kg body weight) with or without EPE administration (140 mg/kg body weight). Oxidative stress biomarkers, inflammatory mediators, steroidogenic gene expression, serum testosterone, sperm parameters, and histopathological alterations were assessed. LC-MS analysis characterized the phytochemical composition of EPE. PPF exposure significantly increased lipid peroxidation and reduced antioxidant enzyme activities, accompanied by downregulation of Nrf2 and its downstream targets. In parallel, NF-κB expression and pro-inflammatory cytokines were elevated. These molecular disturbances were associated with suppression of StAR, SR-B1, CYP11A1, 3b-HSD, and 17b-HSD expression, decreased testosterone levels, reduced sperm count and motility, increased sperm abnormalities, and structural degeneration of seminiferous tubules. EPE administration markedly attenuated oxidative stress, restored Nrf2 signaling, suppressed inflammatory responses, normalized steroidogenic gene expression and testosterone levels, and improved sperm quality and testicular histology. LC-MS profiling revealed a predominance of flavonol glycosides, flavone C-glycosides, flavan-3-ols, and biflavonoids. These findings suggest that EPE mitigates PPF-induced reproductive toxicity through restoration of redox and inflammatory homeostasis.