A green approach for synthesizing zinc oxide nanoparticles utilizing aqueous extract of lemon peel: antibacterial evaluation and in silico analysis

Introduction Green-synthesized metal nanoparticles, primarily derived from plant sources, have attracted interest due to their inherent sustainability. In this study, we reported the green synthesis of zinc oxide nanoparticles (ZnO NPs) using an aqueous extract of dried lemon peel. In addition, antibacterial activity and in silico analysis of the as-prepared ZnO NPs were performed. Methods Different techniques, including X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HR-TEM), selected-area electron diffraction (SAED), Thermogravimetric Analysis (TGA) and Zeta potential were used to confirm the synthesis of ZnO NPs using lemon peel extract. MIC and disk diffusion assays were performed to evaluate the antibacterial activity of the ZnO NPs. In silico target prediction and protein–protein interaction (PPI) network analysis of phytochemical compounds present in the lemon peel extract were performed. Results Multiple characterization techniques demonstrate the production of ZnO NPs from the lemon peel extract as a capping and stabilizing agent. The antibacterial efficacy of ZnO nanoparticles was assessed against six Gram-positive and Gram-negative bacterial strains, with minimum inhibitory concentrations (MICs) varying from 5 to 15 μg/mL. Furthermore, antimicrobial activity was evaluated by well and disc diffusion assays at different concentrations, confirming its antibacterial activity. Biofilm inhibition was observed at concentrations of 50 μg/mL and 75 μg/mL. In addition, in silico target prediction and PPI network analysis of major lemon peel-derived phytochemicals (eriocitrin, hesperidin, and pectin), which may remain associated with the biosynthesized nanoparticles as capping or stabilizing agents, revealed interactions with multiple bacterial proteins, particularly in E . coli , with significant enrichment in nucleotide biosynthesis, fatty acid metabolism, and central carbon metabolism pathways. Discussion Overall, the results suggest that biogenic ZnO NPs exhibit strong antibacterial and antibiofilm activity. Computational analyses further indicate that major lemon peel-derived phytochemicals associated with nanoparticle synthesis may contribute to antibacterial activity through interactions with multiple bacterial metabolic pathways, alongside established ZnO-mediated mechanisms such as reactive oxygen species generation, membrane disruption, and zinc ion release.