Green synthesis of Zinc Oxide nanoflowers using <i>camellia sinensis</i> extract and evaluation of their xenobiotic-like cellular, apoptotic, and inflammatory responses in fibroblast cells

Zinc oxide (ZnO) nanomaterials, acting as engineered xenobiotic-like agents, can induce complex cellular stress and defense responses. This study reports a novel green synthesis of ZnO nanoflowers using <i>Camellia sinensis</i> leaf extract, resulting in a biocompatible nanostructure with a distinctive flower-like morphology.The <i>C. sinensis</i>-mediated synthesis provides a sustainable and reproducible approach for producing stable ZnO nanoflowers. The nanoparticles were thoroughly characterised (hydrodynamic assembly size: 259.3 nm; zeta potential: -32.35 mV; individual nanostructure physical dimensions: ∼38.8 × 138.7 nm), and their biological interactions were evaluated in L929 fibroblasts to assess xenobiotic-like cellular responses.Cytotoxicity was dose- and time-dependent (IC₅₀ = 52.3 µg/mL at 24 h, 14.1 µg/mL at 48 h, and 10.5 µg/mL at 72 h). At a non-toxic IC₅₀ concentration, the nanoflowers induced a transient adaptive stress response, characterised by significant yet reversible upregulation of inflammatory cytokines (IL-1β, IL-10) and key apoptotic regulators (Bax, Bcl-2, and p53).Collectively, this study demonstrates that green-synthesised ZnO nanoflowers trigger moderate, self-resolving apoptotic and inflammatory signalling consistent with a xenobiotic-like adaptive cellular response. These findings highlight the potential of plant-mediated synthesis to engineer ZnO nanostructures with controlled bioactivity, supporting their safer application in biomedical contexts.