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Paul Victor¹, Dronamraju Sarada¹, Kunka Mohanram Ramkumar²

¹Department of Biotechnology, School of Bio-engineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, 603 203, Tamil Nadu, India.

European Journal of Pharmacology

|July 26, 2020

Abstract:

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.

Insights

Diabetic wound healing is challenging due to cellular stress. Bioactive compounds activating Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling show promise in restoring redox balance and promoting tissue repair.

Area of Science:

Biomedical Sciences
Regenerative Medicine
Molecular Biology

Background:

Delayed wound healing in diabetes mellitus is a significant clinical challenge, often exacerbated by elevated cellular stress.
Current therapeutic strategies, including advanced wound dressings and therapies like hyperbaric oxygen, aim to accelerate healing and restore tissue homeostasis.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is identified as a critical regulator of cellular redox balance and antioxidant defense.

Purpose of the Study:

To review strategies for enhancing diabetic wound healing.
To highlight the role of bioactive compounds in activating Nrf2 signaling pathways.
To elucidate how Nrf2 activation revitalizes cellular mechanisms and promotes redox homeostasis in chronic wounds.

Main Methods:

Literature review of studies on wound repair, diabetic complications, and Nrf2 signaling.
Analysis of research on bioactive compounds and their effects on cellular stress and antioxidant production.
Synthesis of findings on Nrf2 activators in the context of diabetic wound healing models.

Main Results:

Nrf2 activation combats oxidative stress by inducing cytoprotective genes and antioxidant production.
Bioactive compounds that activate Nrf2 have demonstrated efficacy in reducing cellular stress and accelerating wound healing processes.
Nrf2 signaling promotes cell proliferation and neovascularization, crucial for tissue regeneration in diabetic wounds.

Conclusions:

Activating Nrf2 signaling presents a promising therapeutic avenue for improving diabetic wound healing.
Bioactive compounds targeting Nrf2 can restore redox homeostasis and enhance tissue repair in chronic wound environments.
Further research into Nrf2-activating compounds could lead to novel treatments for diabetic foot ulcers and other related complications.

Read full analysis

Keywords:

Chronic wounds Nrf2 activators Redox signaling Wound healing

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