Plant - derived zinc oxide nanoparticles as antihyperglycemic: green synthesis, mechanisms, and therapeutic potential

Diabetes mellitus, particularly type 2 diabetes (T2DM), constitutes one of the foremost global health crises of the twenty-first century, affecting approximately 537 million adults worldwide with projections exceeding 780 million by 2045. Conventional pharmacological interventions carry limitations including adverse side effects, progressive loss of efficacy, and high cost, particularly in low- and middle-income contexts. Plant-derived zinc oxide (ZnO) nanoparticles have emerged as a compelling multifunctional alternative, combining the intrinsic bioactivities of botanical extracts with the quantum-level physicochemical properties of nanoscale ZnO. This review focuses on plant-material applications. It critically examines the green synthesis of ZnO nanoparticles using diverse plant sources, the mechanistic basis of their antihyperglycemic activity encompassing enzymatic inhibition, insulin-mimetic Zn²⁺ ion release, reactive oxygen species (ROS) modulation, and glucose transporter type 4 (GLUT4) translocation and their demonstrated efficacy in vitro and in vivo. Furthermore, it addresses current safety considerations, regulatory frameworks, and the integration of computational biology for predictive antihyperglycemic design. The available preclinical evidence indicates that selected, plant-derived ZnO nanoparticle formulations may inhibit key hyperglycemia-associated enzymes (α-amylase, α-glucosidase) with maximum inhibition efficiencies of up to 96% reported under study-specific assay. In addition, these nanoparticles have been associated with reduced oxidative stress in pancreatic β-cells, and enhanced peripheral glucose uptake. These findings suggest that photosynthesised ZnO nanoparticles represent promising preclinical candidates for further investigation. However, further studies are required to establish their long-term safety, pharmacokinetics, reproducibility, and clinical efficacy.