Plant-Mediated Zinc Oxide Nanoparticles From Sideritis syriaca subsp. nusairiensis: A Promising Nano-Enabled Approach...

Sideritis syriaca is a medicinal plant known for its rich phytochemical content and biological potential; however, studies on integrating plant extracts with nanoparticle synthesis and comprehensive bioactivity assessment have been limited. In this study, hydroethanolic extract (SSNE) and zinc nanoparticles (SSNP) were obtained from S. syriaca subsp. nusairiensis. The phytochemical composition of the SSNE was determined using GC-MS/MS and LC-HRMS techniques, while the SSNPs were comprehensively characterized by UV-Vis, FTIR, SEM, TEM, XRD, DLS, and zeta potential analyses. The biological activities of SSNE and SSNPs were evaluated in terms of antioxidant, antibacterial, antibiofilm, anti-inflammatory, antiproliferative, enzyme inhibitor, and DNA protective effects. Also, network pharmacology and molecular docking analyses were applied to elucidate their potential mechanisms of action. The results showed that α-pinene (33.54%), β-pinene (28.43%), and β-caryophyllene (17.59%) were the main volatile compounds in GC-MS/MS analysis, while chlorogenic acid (7127.073 µg/g extract) and quinic acid (6161.663 µg/g extract) were the dominant phenolic compounds in LC-HRMS analysis. SSNP demonstrated significantly higher biological activity compared to SSNE and standard compounds, particularly in antioxidant, enzyme inhibition, and anti-inflammatory (13.82 µg/mL) tests. Specifically, SSNE showed stronger α-amylase inhibition (1.25 µg/mL) compared to acarbose (55.22 µg/mL). Also, SSNP demonstrated strong antibacterial and antibiofilm (51%) activity, particularly against Pseudomonas aeruginosa, and exhibited antiproliferative effects (20.87 µg/mL) against HT29 cells. These findings demonstrate that SSNPs synthesized using a green approach possess enhanced biological activities and favorable physicochemical properties, and may be promising candidates for application in pharmaceutical and food-related systems. Thus, this study presents an integrated approach combining phytochemical profiling, green nanoparticle synthesis, and multi-level biological evaluation.