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.