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.
Mendonce et al. (Sun,) studied this question.