Topical treatment with anti-oxidants and Au nanoparticles promote healing of diabetic wound through receptor for advance glycation end-products

Impairment in diabetic wound healing constitutes an enormous biomedical burden. The receptor for advanced glycation end-products (RAGE) expression in the diabetic cutaneous wound may play a key role. However, the relationship between RAGE expression and topical application of anti-oxidant agents with gold nanoparticles (AuNP) in cutaneous diabetic wounds remains unclear. We tested the 3–5 nm AuNP, epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) could change the RAGE expression and be helpful in diabetic wound. The mixture of AuNP+EGCG+ALA (AuEA) significantly attenuated the AGE-induced RAGE protein expression in fibroblasts (Hs68). Topical EGCG+ALA (EA) and AuEA application accelerated wound healing on diabetic mouse skin and decreased the RAGE expression. Vascular endothelial growth factor but not angiopoietin-1 significantly increased after EA or AuEA treatment for 7 days. Angiopoietin-2 significantly decreased at day 7 in AuEA group. Furthermore, immunoblotting of diabetic wound tissue showed significant decrease of CD68 expression from day 3 to day 7. The results suggest that combination of AuNP, EGCG, and ALA significantly accelerated diabetic cutaneous wound healing through angiogenesis regulation and anti-inflammatory effects. Blockade of RAGE by anti-oxidant agents and nanoparticles may restore effective wound healing in diabetic ulcer.

Graphical abstractAu nanoparticles (3–5 nm) (Fig. A) combined with epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) significantly accelerated diabetic cutaneous wound healing in mice (Fig. B) by decreasing RAGE protein expression (Fig. C) and angiogenesis regulation (Fig. D). EA: EGCG+ALA; AuEA: AuNP+EGCG+ALA. ∗p < 0.01 when compared to DM or vehicle group. +p < 0.05 AuEA group compared to vehicle group.Figure optionsDownload full-size imageDownload high-quality image (38 K)Download as PowerPoint slide