Polyphenolic oligomer-derived multienzyme activity for the treatment of ischemic Stroke through ROS scavenging and blood–brain barrier restoration

Oxidative stress and blood-brain barrier (BBB) injury are two major stress disorders before and after ischemic stroke (IS) therapy. The intense inflammatory response also causes damage to nerve cells, affecting the repair of brain tissue. In this study, polyphenolic nanoparticles (PPNs) with strong free radical scavenging ability were designed to treat IS multimodally. To investigate the mechanism of polyphenolic polymerization, solid nanoparticles were synthesized using four kinds of polyphenol compounds as the basic unit under the control of temperature. The form of polymerization between monomers with different structures led to changes in the chemical properties of the corresponding nanoparticles as well as the antioxidant capacity at the cellular level. Particularly, PPNs can significantly improve cerebral infarction and penetrate and repair the BBB, and even downregulate levels of inflammatory cytokines. Molecular signaling pathway studies have shown that PPNs can provide comprehensive treatment of IS by promoting the expression of tight junction protein and enhancing the activity of antioxidant enzymes. Therefore, PPNs combined with the antioxidant, anti-inflammatory and BBB repair ability not only provide a perfect therapeutic pathway but also give ideas for the development of natural material carriers that have a wide application prospect.