Moringa oleifera leaf nanoemulsion attenuates polystyrene nanoplastic-induced hepatotoxicity and dysregulation of hepatic glucose metabolism in rats

Background and Aim: Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that can induce hepatic oxidative stress, inflammation, apoptosis, and metabolic dysfunction. Although Moringa oleifera leaves contain diverse antioxidant and hepatoprotective phytochemicals, conventional extracts may have limited aqueous solubility and oral bioavailability. This study aimed to develop a M. oleifera leaf nanoemulsion and evaluate its protective effects against PS-NP-induced hepatotoxicity and dysregulation of hepatic glucose metabolism in rats. Materials and Methods: Forty-eight male Wistar rats were randomly assigned to six groups (n = 8 per group): normal control, PS-NP control receiving 200 μg/kg body weight (BW)/day, positive control receiving PS-NPs with quercetin at 20 mg/kg BW/day, and three treatment groups receiving PS-NPs with M. oleifera leaf nanoemulsion at extract-equivalent doses of 10, 20, or 40 mg/kg BW/day for 28 days. The extract and nanoemulsion were characterized using phytochemical analyses, antioxidant assays, Fourier-transform infrared spectroscopy, dynamic light scattering, and transmission electron microscopy. Hepatoprotective effects were assessed using serum liver enzymes, hepatic antioxidant, inflammatory, and apoptotic markers, histopathology, quantitative gene expression analysis, and exploratory molecular docking. Results: The nanoemulsion had a mean hydrodynamic diameter of 72.1 nm, a polydispersity index of 0.33, and a zeta potential of −36.09 mV. PS-NP exposure increased liver injury biomarkers and histopathological damage, suppressed superoxide dismutase and catalase, and increased tumor necrosis factor-α, interferon-γ, caspase-9, and caspase-3. PS-NPs also downregulated Slc2a2, Pklr, and Gys2 and upregulated Pck1. Nanoemulsion treatment attenuated these biochemical, histological, inflammatory, apoptotic, and transcriptional alterations, with the most consistent protective responses observed at 10–20 mg/kg. Exploratory molecular docking indicated potential multitarget interactions of selected phytoconstituents, particularly β-sitosterol. Conclusion: Moringa oleifera leaf nanoemulsion attenuated PS-NP-induced hepatotoxicity and partially normalized glucose metabolism-related gene expression. The findings provide experimental proof-of-concept for nanoemulsion-based delivery of M. oleifera phytoconstituents against nanoplastic-associated liver injury, although further pharmacokinetic and dose–response studies are warranted. Keywords: antioxidant defense, glucose metabolism, hepatotoxicity, Moringa oleifera, nanoemulsion, oxidative stress, polystyrene nanoplastics, Wistar rats.