Unveiling Wound Healing Properties of Biostimulated Walnut Kernel Extracts via Epithelial Mesenchymal Transition: Switching a Nutritional Matrix into a Therapeutic Remedy

Walnuts (Juglans regia L.) are recognized for their rich nutritional profile and health-promoting properties. This study investigates the impact of biostimulation, via wood distillate application, on the chemical composition and therapeutic potential of walnut kernels, focusing on their wound healing activity. Biostimulated walnuts showed enhanced levels of phenolic compounds including antioxidants, sugars, and amino acids compared to untreated or agrochemically treated controls. Phytocomplexes extracted from walnut kernels using green methodologies were tested on human keratinocytes (HaCaT), revealing pro-migratory effect, boosted by biostimulation. Molecular analyses demonstrated the activation of epithelial–mesenchymal transition (EMT) pathways, marked by downregulation of epithelial markers and upregulation of mesenchymal genes such as MMP3, MMP9, vimentin, and SMAD3. Furthermore, a synergistic effect was observed between extracts derived from biostimulated kernels and manuka honey in promoting wound closure. These findings suggest that kernels from biostimulated walnuts may serve as functional foods, paving the way for their use in regenerative medicine.