Curcumin modulates NF-κB and Nrf2 pathways to mitigate inflammation, oxidative stress, and virulence in Pseudomonas aeruginosa-infected bronchial epithelial cells.

Pseudomonas aeruginosa pneumonia is characterized by excessive inflammation, oxidative damage, and virulence-driven epithelial injury. Targeting host inflammatory and antioxidant pathways, alongside bacterial virulence factors, may offer a complementary strategy to mitigate infection-induced damage. Curcumin, a bioactive compound from Curcuma longa, possesses established anti-inflammatory and antioxidant properties, but its effects on epithelial responses during bacterial infection remain incompletely defined. This study evaluated the impact of curcumin on NF-κB and Nrf2 signaling, inflammatory and oxidative responses, bacterial virulence, and epithelial repair in a cell-based model of P. aeruginosa–induced airway injury. Human bronchial epithelial BEAS-2B cells were pretreated with curcumin (10 µM) prior to infection with P. aeruginosa (1 × 10⁷ CFU/mL; MOI = 10). Cell viability, oxidative stress, cytokine production, bacterial load, and epithelial regeneration were assessed using MTT, DCFDA, qPCR, ELISA, while Western blotting and confocal microscopy characterized molecular and morphological changes. Curcumin pretreatment improved cell viability (~ 87% vs. ~64% in infected), attenuated NF-κB activation and cytokine expression, and enhanced Nrf2 pathway activity (HO-1, NQO1). Reactive oxygen species levels were reduced (~ 250% to ~ 140%), LasR expression and intracellular bacterial burden were decreased, and epithelial wound closure were partially restored compared with infected controls. Collectively, these findings indicate that curcumin modulates inflammatory, oxidative, and virulence-associated pathways and supports epithelial repair in P. aeruginosa-infected bronchial epithelial cells, suggesting potential relevance as a host-directed adjunct rather than a direct antimicrobial agent.