# Amphiphilic Macromolecular Dendritic Antioxidants with Surfaces Coated in Hybrid Phenolic Units That Provide Anti-Inflammatory Properties

**Authors:** Blessed Agbemade, Fati Haruna, Aundrea Stengard, Nanzhu Li, Cal M. Butts, Rebecca Uzarski, Choon Young Lee

PMC · DOI: 10.1021/acsapm.5c04280 · ACS Applied Polymer Materials · 2026-02-20

## TL;DR

Researchers developed new antioxidant molecules that are more effective at fighting free radicals and reducing inflammation in cells.

## Contribution

Amphiphilic dendritic antioxidants with hybrid phenolic surfaces show superior antioxidant and anti-inflammatory performance.

## Key findings

- G2 and G1 antioxidants were 156 and 77 times more effective than syringaldehyde in scavenging free radicals.
- G1 reduced NO and IL-6 levels by 76% and 100%, respectively, in inflamed macrophages.
- G1 showed strong anti-inflammatory effects without significant toxicity at lower concentrations.

## Abstract

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.

## Linked entities

- **Chemicals:** syringaldehyde (PubChem CID 8655), pyridoxal (PubChem CID 1050), 2,2-diphenyl-1-picrylhydrazyl (PubChem CID 2735032), NO (PubChem CID 24822), IL-6 (PubChem CID 165368475)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** inflammatory cytokine (MESH:D000080424), Inflammation (MESH:D007249)
- **Chemicals:** syringaldehyde (MESH:C069665), reactive oxygen species (MESH:D017382), NO (MESH:D009614), lipopolysaccharide (MESH:D008070), 2,2-diphenyl-1-picrylhydrazyl (MESH:C004931), pyridoxal (MESH:D011730)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12993807/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12993807/full.md

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Source: https://tomesphere.com/paper/PMC12993807