Phyto-Mediated Zinc Oxide Nanoparticles from Raphanus sativus (L.): Metabolomic Insights, Gastroprotective Potential, and Docking-Supported Evidence

This study aimed to synthesize zinc oxide nanoparticles (ZnO-NPs) via a green sustainable approach using <i>Raphanus sativus</i> (L.) root extract and evaluate their gastroprotective effect against ethanol-induced gastric injury in rats. ZnO-NPs were characterized through UV-Vis spectroscopy, FT-IR, TEM, zeta potential analysis, and XRD. LC- MS-coupled metabolic profiling was employed to identify different phytochemical compounds in the plant. Oxidative stress biomarkers (GSSG, GPX, and CAT), gastric secretions (gastrin and histamine), inflammatory cytokines (TNF-α and NF-κB), and molecular markers (MMP-10 and pERK1/2) were evaluated. Treatment with ZnO-NPs and plant extract restored antioxidant enzyme activity in a dose-dependent manner and decreased oxidative and inflammatory markers. Histopathological and histochemical analyses confirmed the protection of the gastric mucosa. The ZnO-NPs at (200 mg/kg), showed superior efficacy over the extract and, in some cases, displayed equivalent or enhanced effects relative to the reference drug omeprazole. In silico findings support the gastroprotective potential of the plant by demonstrating strong binding associations for major phytochemicals. This paper highlights that green-synthesized ZnO-NPs exhibit a significant gastroprotective effect through the modulation of oxidative stress and inflammatory pathways, indicating their promise as a safe and effective alternative treatment for gastric ulcers.