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<p>Diabetic foot infection (DFI) leads to delayed wound healing in diabetic patients and is a significant cause of foot amputation. Others and we reported the efficient use of green-synthesized nanoparticles in promoting skin wound healing. In this research, we targeted to green-synthesized silver nanoparticles (AgNPs) using aqueous extract of the wild-plant <i>Farsetia aegyptia</i> (FA-AgNPs) and to investigate their antibacterial effect and wound-healing capacity in DFI rat model. Gas chromatography–mass spectrometry revealed a high concentration of biologically active phytochemicals with antibacterial and antidiabetic properties. Several characterization techniques were employed to confirm the biosynthesis of FA-AgNPs. Interestingly, FA-AgNPs showed significant antibacterial action against the multidrug-resistant DFI-derived <i>Staphylococcus aureus</i>. Mechanistic studies revealed that FA-AgNPs exerted antibacterial action via increasing ROS accumulation, membrane leakage, permeability, and distraction of surface structure in the DFI <i>S. aureus</i>. Several anti-biofilm tests and microscopic studies confirmed that FA-AgNPs effectively suppress biofilm formation. The wound-healing activity of FA-AgNPs was explored in DFI rat model infected with <i>S. aureus</i> isolated from DFI patients. Histological and immunohistochemical analysis of skin wound revealed enhanced wound-healing features in the FA-AgNPs-treated DFI group, including increased cellular proliferation, reduced inflammation, increased collagen deposition, and angiogenesis. In addition, FA-AgNPs significantly inhibited bacterial burden in foot ulcers. The mode of FA-AgNPs action to enhance wound healing in DFI model was found to be mediated by activating transforming growth factor β1(TGF-β1)/Smad pathway and increasing the expression of angiogenesis markers vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor β (PDGF-β). In addition, FA-AgNPs displayed anti-inflammatory effect by inhibiting the Toll-like receptor 4/Nuclear factor kappa B (TLR-4/NF-κB) signaling as determined by western blot examination. In conclusion, FA-AgNPs could provide a novel green therapeutic strategy for promoting wound healing in DFI.</p>

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Phytofabricated Farsetia aegyptia-derived silver nanoparticles mediate antibacterial and wound-healing activities in diabetic foot infection rat model

  • 期刊论文

  • 发表日期：

    2025年6月3日

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  • Enas M. Ali,
  • Peramaiyan Rajendran,
  • Basem M. Abdallah

摘要

Diabetic foot infection (DFI) leads to delayed wound healing in diabetic patients and is a significant cause of foot amputation. Others and we reported the efficient use of green-synthesized nanoparticles in promoting skin wound healing. In this research, we targeted to green-synthesized silver nanoparticles (AgNPs) using aqueous extract of the wild-plant Farsetia aegyptia (FA-AgNPs) and to investigate their antibacterial effect and wound-healing capacity in DFI rat model. Gas chromatography–mass spectrometry revealed a high concentration of biologically active phytochemicals with antibacterial and antidiabetic properties. Several characterization techniques were employed to confirm the biosynthesis of FA-AgNPs. Interestingly, FA-AgNPs showed significant antibacterial action against the multidrug-resistant DFI-derived Staphylococcus aureus. Mechanistic studies revealed that FA-AgNPs exerted antibacterial action via increasing ROS accumulation, membrane leakage, permeability, and distraction of surface structure in the DFI S. aureus. Several anti-biofilm tests and microscopic studies confirmed that FA-AgNPs effectively suppress biofilm formation. The wound-healing activity of FA-AgNPs was explored in DFI rat model infected with S. aureus isolated from DFI patients. Histological and immunohistochemical analysis of skin wound revealed enhanced wound-healing features in the FA-AgNPs-treated DFI group, including increased cellular proliferation, reduced inflammation, increased collagen deposition, and angiogenesis. In addition, FA-AgNPs significantly inhibited bacterial burden in foot ulcers. The mode of FA-AgNPs action to enhance wound healing in DFI model was found to be mediated by activating transforming growth factor β1(TGF-β1)/Smad pathway and increasing the expression of angiogenesis markers vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor β (PDGF-β). In addition, FA-AgNPs displayed anti-inflammatory effect by inhibiting the Toll-like receptor 4/Nuclear factor kappa B (TLR-4/NF-κB) signaling as determined by western blot examination. In conclusion, FA-AgNPs could provide a novel green therapeutic strategy for promoting wound healing in DFI.