Pharmacological activation of Nrf2 promotes wound healing

Wound repair and regeneration is a complex orchestrated process, comprising several phases interconnecting various cellular events and triggering multiple intracellular molecular pathways in damaged cells and tissues. In several metabolic disorders including diabetes mellitus, delay in wound healing due to elevated levels of cellular stress poses a key challenge. Several therapeutic wound dressing materials and strategies including hyperbaric oxygen therapy and negative pressure wound therapy have been developed to accelerate repair and restore cellular homeostasis at the wound site. Further, tremendous progress has been made in identification of transcriptional regulators involved in the process of wound healing. Nuclear factor erythroid 2-related factor 2 (Nrf2), a redox sensitive transcription factor, is the key regulator of intracellular redox homeostasis which induces the expression of cytoprotective genes and increases the production of antioxidants that scavenge free radicals. Activators of Nrf2 have been reported to combat oxidative stress and enhance the process of wound healing in several pathophysiological conditions, including diabetes and its complications such as diabetic foot ulcer, and chronic kidney disease, and diabetic nephropathy. Several bioactive compounds have been reported to reduce cellular stress, and thus accelerate cell proliferation, neovascularization results in repairing damaged tissues by the activation of the transcription factor, Nrf2. This review is focused on the strategies for diabetic wound healing and the highlights the role of bioactive compounds that activate the Nrf2 signaling and revitalize the cellular and molecular mechanism in the chronic wound niche, regulate and restore redox homeostasis thereby promoting wound repair and regeneration.