Nature-inspired ZnO nanoparticles: unlocking the biomedical potential of <i>Glycyrrhiza glabra</i> -mediated green synthesis through <i>in vitro</i> and <i>in silico</i> approaches

In this research work, the aqueous root extract of <i>Glycyrrhiza glabra</i> (<i>G. glabra</i>) was used to synthesize phytoconstituent-coated zinc oxide nanoparticles (ZnONPs) for the first time. The plant extract served as a reducing and coating/stabilizing agent. The alteration in the physicochemical properties and biomedical potential of the synthesized ZnONPs with an increase in the volume of <i>G. glabra</i> extract was investigated, making this study different from others. X-ray diffraction (XRD) analysis confirms that the average crystallite size of the nanoparticles decreased with an increase in the plant extract volume. Field-emission scanning electron microscopy (FESEM) analysis confirmed the formation of uniform spherical particles for all three samples, while energy-dispersive X-ray (EDX) analysis revealed their elemental composition. The samples showed excellent antibacterial activity against Gram-positive <i>Streptococcus mutans</i> and Gram-negative <i>Escherichia coli</i> with the highest zone of inhibition values of 19.33 ± 0.47 and 25 ± 0.81 mm, respectively. <i>In silico</i> molecular docking studies were also performed against two different receptors, <i>i.e.</i>, DNA gyrase B (<i>E. coli</i>) and antigen-I/II carboxy-terminus (<i>S. mutans</i>) proteins with several phytoconstituents (identified through gas chromatography-mass spectroscopy (GC-MS) analysis). Among the four phytoconstituents, 9,12-octadecadienoic acid (<i>Z</i>,<i>Z</i>)- (-5.5, and -4.8 kcal mol^-1) and <i>n</i>-hexadecanoic acid (-5.5 and -4.5 kcal mol^-1) exhibited the highest binding affinity. The molecular docking outcome demonstrates good agreement with the <i>in vitro</i> result. Additionally, the cell viability of the as-synthesized ZnONPs against a normal cell line (HaCaT) was >95% compared to the cell viability against cancer cells (69.5% ± 3.8%), which indicates that the sample has higher selectivity towards cancer cells. Subsequently, the minimal toxicity of the phytochemical-coated ZnONPs enhances their suitability across diverse biomedical fields, especially in combating bacterial infections.