An in-silico approach to evaluate the diabetic wound healing potential of phenylethanoid glycoside in inhibiting the receptor for advanced glycation endproducts (RAGE)

Diabetes mellitus (DM) is a chronic metabolic disorder and is associated with impaired wound healing. Non-healing leg and foot ulcers are a frequent significant consequence of diabetes and are caused by a combination of inadequate tissue perfusion, suppression of re-epithelialization, and poor collagen production. Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand cell surface molecule that belongs to the immunoglobulin superfamily is crucial in the pathophysiology of poor wound healing in diabetics. By inhibiting RAGE, a chronic non-healing wound is more likely to undergo angiogenesis, enhance blood supply to hypoxic areas of the wound and decrease in the pro-inflammatory reaction and pro-apoptotic signaling. Phenylethanoid glycosides (PhGs) are a class of natural glycosides, which possesses anti-diabetic, wound healing, antimicrobial, anti-inflammatory, and antioxidant properties. Echinacoside, a phenylethanoid glycoside has a promising role in wound healing by enhancing angiogenesis, promoting keratinocyte migration and proliferation, and enhancing neutrophil and macrophage activity. Consequently, a molecular docking was performed to assess the interaction between Echinacoside and the RAGE receptor (PDB ID: 6VXG). The ligand and receptor had a strong binding interaction, as indicated by the lowest binding energy, which was found to be -6.1 kcal/mol. To further assess the activity of Echinacoside in diabetic wound healing, in-vitro and in-vivo studies are needed.