Protective effect of a novel metal-phenolic network composite against ultraviolet-induced skin damage by modulating MAPK/AP-1/NF-κB signaling pathways and attenuating oxidative stress in human keratinocytes.

Summary

An MPN-based hair dye (Melamax) provided robust photoprotection: it reduced UV-induced ROS, downregulated MMP-1/MMP-3 and p16 while restoring TIMP-1, suppressed inflammatory cytokines, and upregulated antioxidant and hydration-related genes. Mechanistically, it inhibited ERK/JNK/p38 phosphorylation and downstream AP-1 and NF-κB activation in keratinocytes and mitigated UV-driven transcriptional changes in a 3D skin model.

Key Findings

• Melamax reduced UV-induced ROS in HaCaT keratinocytes and mitigated oxidative stress.
• It downregulated MMP-1/MMP-3 and p16 and restored TIMP-1 expression.
• Inflammatory cytokines (IL-6, IL-1β, IL-8, TNF-α) were markedly attenuated.
• Inhibited ERK/JNK/p38 phosphorylation and suppressed AP-1 and NF-κB activation; transcriptomics in a 3D skin model showed suppression of matrix degradation, inflammation, and oxidative stress pathways.

Clinical Implications

Although preclinical, these data support developing hair dyes that also confer skin photoprotection, potentially reducing photoaging and irritation; translational studies and safety assessments are needed before clinical use.

Limitations

• Preclinical in vitro study without in vivo or human clinical validation.
• Long-term safety, skin penetration, and real-world UV exposure scenarios were not assessed.

Future Directions

Evaluate in animal models and human studies, assess safety/irritancy and pharmacodynamics, and optimize formulations for durable photoprotection.