Antimicrobial, antibiofilm, angiogenesis, anti-inflammatory, and wound healing activities of zinc nanoparticles green synthesized using Ferula macrecolea extract

Objective: To assess the antimicrobial, antibiofilm, anti-inflammatory, angiogenic, and wound healing activities of zinc nanoparticles (ZNPs) green synthesized using Ferula macrecolea extract. Methods: The green synthesis was conducted using the precipitation method. Then, the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm inhibition concentration 50% (MBIC50) of ZNPs against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) were evaluated. The effects of ZNPs on the gene expressions of Staphylococcus spp. [intracellular adhesion A (icaA) and D (icaD)] and P. aeruginosa (rhlI and rhlR) were investigated using quantitative real-time PCR. In addition, the effects of ZNPs on wound healing, angiogenesis, and anti-inflammatory markers were assessed. Results: The green-synthesized ZNPs demonstrated significant antimicrobial efficacy against S. aureus and P. aeruginosa. The biofilm formation in S. aureus and P. aeruginosa was also inhibited by ZNPs with MBIC50 values of 3.30 mu g/mL and 2.08 mu g/mL, respectively. Additionally, ZNPs downregulated the expression of biofilm-related genes icaA, icaD, rhlI, and rhlR in the tested bacteria. They also demonstrated promising in vitro wound healing effects by promoting fibroblast cell proliferation and wound closure in a dose-dependent manner. A significant increase in the expression of HLA-G5 and VEGF-A genes as well as a marked decrease in the expression of NF-kappa B, IL-1 beta, and TNF-alpha genes were observed in cells treated with ZNPs compared to the control group (P<0.05). Conclusions: ZNPs display promising antibacterial effects against S. aureus and P. aeruginosa and wound-healing effects by inhibiting biofilm formation, inducing angiogenesis, and reducing inflammation. However, further studies must be conducted to specify the accurate mechanisms of action and toxicity of ZNPs.