Amphiphilic Macromolecular Dendritic Antioxidants with Surfaces Coated in Hybrid Phenolic Units That Provide...

Excess free radicals cause oxidative stress, which damages cells and triggers inflammation. Inflammation generates more radicals, creating a self-perpetuating cycle that contributes to many human diseases. Antioxidants can neutralize radicals and prevent inflammation. Two unique amphiphilic dendritic antioxidants, Generation 1 (G1) and Generation 2 (G2), were developed, each featuring an equal ratio of hydrophobic syringaldehyde to water-soluble pyridoxal on their surfaces. G1 carries six units of each component, whereas G2 contains 12 units of each. In the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay, G2 and G1 exhibited IC50 values of 1.28 and 2.6 μM, respectively. In comparison, syringaldehyde and pyridoxal exhibited significantly higher IC50 values of 200 and 16500 μM, respectively. G2 and G1 are 156 and 77 times more effective than syringaldehyde and 12890 and 6346 times more potent than pyridoxal, highlighting the benefits of building antioxidants within dendritic frameworks. In cell viability assays with RAW 264.7 macrophages, G1 only reduced cell viability at the highest tested concentration (323 μM), while G2 induced a statistically significant decrease starting at 11.3 μM. In lipopolysaccharide-stimulated macrophages, G1 at 32.3 μM showed strong anti-inflammatory effects, lowering NO levels by 76% and IL-6 levels by 100%, indicating that G1 can produce its potent anti-inflammatory effects via dual mechanisms: scavenging reactive oxygen species and reducing pro-inflammatory cytokine production. G2 had limited effects at its nontoxic concentrations.