Ameliorating effects of Stevia extract combined with green-synthesized silver nanoparticles coated with soy soluble polysaccharides on diabetic wounds in a rat model

Abstract

The use of silver nanoparticles (AgNPs) as a new treatment for diabetic wound (DW) healing is limited due to cytotoxicity. This study evaluated the potential of a green approach using Stevia extract (SE) to synthesize AgNPs coated with soy soluble polysaccharides (SSPS-gAgNPs) to accelerate wound healing treatment. The SSPS-gAgNPs were characterized by TEM, XRD, DLS, and FTIR spectroscopy. Their cytotoxic effect was evaluated using the MTT assay. The effect of SSPS-gAgNPs and SE on in vivo DW healing and MMP-9, TIMP-1 and b-FGF mRNA expression was evaluated. On day 14 post-wounding, the wound area (mm²) decreased in the presence of SSPS-gAgNPs alone (65.93 ± 4.39; P = 0.000) or SE alone (73.31 ± 8.56; P = 0.000) or a combination of SSPS-gAgNPs and SE (45.93 ± 8.14; P = 0.000) compared with the wound area in untreated control (107 ± 8.72). In addition, the collagen deposition percentage was significantly higher in the SSPS-gAgNPs/SE combination (47.05% ± 3.070%) than in SSPS-gAgNPs alone (36.55% ± 3.20%; P < 0.01) or SE (21.47% ± 2.74%; P < 0.0001) alone. In contrast, the lymphocyte number per area (mm²) decreased in response to the SSPS-gAgNPs/SE combination (78.33 ± 9.50) compared with SSPS-gAgNPs alone (143.3 ± 11.72; P < 0.01). The combination of SSPS-gAgNPs and SE showed a greater effect on increasing b-FGF and TIMP-1 expression and reducing MMP-9 expression than SSPS-gAgNPs or SE alone. Taken together, the findings reveal that SSPS-gAgNPs combined with SE have a considerable ability to accelerate the healing of DWs. Therefore, this combination may be an alternative therapy to improve the outcomes of DWs.