Dietary Zeaxanthin Attenuates Cigarette Smoke-Induced COPD by Suppressing ERK-Driven Apoptosis.

BACKGROUND

Dietary zeaxanthin's role in COPD remains underexplored.

METHODS

A multi-dimensional approach integrating NHANES epidemiological data, multi-omics analyses (network pharmacology, transcriptomics, molecular docking), and experimental validation in a CSE-induced mouse model and HBE cells.

RESULTS

NHANES analysis revealed an inverse association between zeaxanthin intake and COPD risk. Multi-omics identified MAPK1 (ERK2) as a core target, with molecular docking predicting favorable zeaxanthin-MAPK1/MAPK3 interactions. Zeaxanthin alleviated emphysema, improved lung function, and reduced apoptosis/inflammation in vivo, and protected HBE cells in vitro. Mechanistically, it dose-dependently inhibited ERK phosphorylation and downstream cleaved caspase-3 activation. PMA-mediated reactivation of ERK partially reversed the anti-apoptotic effect of zeaxanthin.

CONCLUSION

Dietary zeaxanthin protects against COPD by suppressing the ERK-mediated apoptotic pathway, supporting its potential as a nutritional intervention.