Elia Ranzato, Simona Martinotti
Traditional wound therapies continue to be predominantly exogenous and address extracellular causes of the pathology without addressing the impaired function of cellular pathways that are trapped in the state of constant inflammation. The present review explores a novel putative nutriepigenetic framework, discussing how the honey matrix could act as a proposed modulator of the altered epigenetic landscape in non-healing ulcers. Honey contains a complex mixture of bioactive agents (polyphenols, flavonoids, and plant-derived xenomiRs) that are hypothesized to interact with multiple chromatin control points simultaneously. We discuss models wherein honey-induced aquaporin-mediated H2O2 influx and intracellular calcium transients may correlate with SIRT1/SIRT6 modulation and CRM1-mediated nuclear export of Class IIa HDACs. This review evaluates whether such multi-target signaling could foster chromatin relaxation to support gene expression required for cell migration and tissue remodeling.