Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.

Diabetic foot ulcer (DFU) is one of the most common serious complications of diabetes mellitus and often results in amputation. This complication affects 15% of individuals with diabetes over their lifetime. This review investigates the role of epigenetic modifications in DFUs, as many epigenetic mechanisms contribute to the underlying pathogenesis of diabetes and its complications, including DFUs. Therefore, initiatives aimed at understanding these epigenetic mechanisms may represent a paradigm shift in diagnosing and treating DFUs. Molecular-level studies have been conducted to identify the clinical manifestations of epigenetics in diabetes and its associated complications, such as DFU. This review synthesizes recent literature on epigenetic mechanisms contributing to diabetic foot ulcer (DFU) pathogenesis and explores the therapeutic potential of natural compounds targeting these mechanisms. Through a structured search of databases including PubMed and Scopus, we identified key natural agents, such as curcumin and resveratrol, that modulate DNA methylation, histone modifications, and non-coding RNAs. Natural compounds, which are bioactive ingredients derived from natural organisms, may serve as lead molecules and promising drug candidates, offering an excellent alternative to synthetic drugs for managing and alleviating DFUs and related complications. These natural compounds exhibit pleiotropic activities, including anti-inflammatory and antimicrobial effects, stimulation of angiogenesis, antioxidant activity, facilitation of fibroblast migration, as well as the promotion of cytokines and growth factors; therefore, they hold significant potential as valuable adjuncts to conventional therapy.