Regulation of NF‐κB and MAPK Signaling Pathways in Diabetic Wound Healing by Plant‐Derived Metabolites and Nanoparticles

Chronic inflammation, poor angiogenesis, and delayed tissue regeneration make diabetic wound healing a significant clinical challenge. Diabetes often dysregulates the NF-κB and MAPK signaling pathways, essential for controlling inflammation and cellular repair, leading to chronic wound conditions. Recent advancements suggest combining nanoparticles with plant-derived secondary metabolites as a promising therapeutic approach. Nanoparticles, including metal- and polymer-based types, exhibit antibacterial, anti-inflammatory, and pro-angiogenic effects. They accelerate wound closure, promote cellular proliferation, and modulate inflammatory mediators by targeting the NF-κB and MAPK pathways. Plant secondary metabolites, such as flavonoids, alkaloids, and terpenoids, complement these effects through NF-κB inhibition and MAPK activation, enhancing anti-inflammatory and pro-repair mechanisms. The synergy between nanoparticles and metabolites amplifies the benefits of tissue regeneration, angiogenesis, and inflammation reduction, improving therapeutic outcomes. However, challenges such as nanoparticle-induced cytotoxicity, persistent inflammation, and interference with normal cellular functions remain. Optimizing nanoparticle dosage, developing biodegradable materials, and combining them with plant-derived compounds are essential strategies to mitigate these risks. This review highlights the potential of integrating plant metabolites with nanoparticles to improve diabetic wound healing while addressing associated limitations.