Green-Synthesized Silver Nanoparticles from Zingiber officinale: Physicochemical Characterization, Antibacterial Activity, and TMPRSS2-Modulating Potential.

In this study, green-synthesized silver nanoparticles derived from Zingiber officinale (G-AgNPs) were investigated as potential modulators of transmembrane serine protease 2 (TMPRSS2), a host-associated protease involved in viral entry mechanisms. Before nanoparticle synthesis, the phytochemical composition of ginger extract was analyzed using high-performance liquid chromatography (HPLC) with photodiode array detection. Silver nanoparticles were synthesized using aqueous ginger extract as a reducing and stabilizing agent. The nanoparticles were characterized by ultraviolet-visible spectroscopy (UV-Vis.), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta potential analysis, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The synthesized silver nanoparticles exhibited a face-centered cubic (fcc) crystalline structure, nanoscale particle size distribution, and moderate colloidal stability. Transmission electron microscopy revealed predominantly quasi-spherical nanoparticles with an average diameter of 10.61 ± 1.31 nm, while X-ray diffraction indicated an average crystallite size of 15.28 ± 5.48 nm. Biological evaluation demonstrated robust, broad-spectrum antibacterial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, with distinct susceptibility profiles. Minimum Inhibitory Concentration (MIC) values were 3.125 µg/mL and 12.5 µg/mL, and Minimum Bactericidal Concentration (MBC) values were 6.25 µg/mL and 25.0 µg/mL, respectively. Cell culture assays confirmed high cytocompatibility with L929 fibroblasts at all tested concentrations. In a fluorometric enzyme assay, the silver nanoparticles inhibited TMPRSS2 activity in a concentration-dependent manner, achieving 51.24% inhibition at 100 µg/mL and an estimated IC50 of 40.06 µg/mL. Although the inhibitory activity was lower than that of Camostat, the findings suggest that ginger-mediated silver nanoparticles represent promising plant-based nano-bioactive systems for further investigation of TMPRSS2 modulation.