Association between polyphenols and inhalation-induced oxidative stress in chronic lung diseases: A systematic review

Chronic respiratory diseases associated with inhalation exposure represent a notable global health burden, and are characterized by persistent oxidative stress and inflammation. Plant-derived polyphenols may serve as modulators of redox-sensitive signaling pathways; however, their clinical relevance in inhalation-associated lung disease remains unclear. The present systematic review evaluated the effects of polyphenols on oxidative, inflammatory and clinical outcomes in chronic lung diseases associated with inhalation-induced oxidative stress. P`ubMed, Cochrane Library and Web of Science were searched up to January 2026 for experimental and clinical studies investigating plant-derived polyphenols in inhalation-associated lung injury or chronic airway disease. Eligible studies included in vitro studies, animal models and randomized clinical trials reporting oxidative stress, and inflammatory, functional or structural outcomes. Risk of bias was assessed using Risk of Bias 2 and Systematic Review Center for Laboratory Animal Experimentation tools. Due to notable heterogeneity between studies, findings were synthesized narratively. Preclinical studies consistently demonstrated attenuation of oxidative damage, suppression of inflammatory signaling and enhancement of endogenous antioxidant defenses, typically involving activation of nuclear factor erythroid 2-related factor 2 and modulation of NF-κB pathways. Structural and histopathological improvements were also reported across multiple exposure models. Clinical findings were more heterogeneous. Although several trials reported improvements in oxidative and inflammatory markers or symptom-associated outcomes, effects on spirometric parameters remained inconsistent. Overall, polyphenols demonstrate promising redox-modulating effects in experimental models of inhalation-induced lung injury; however, clinical trials remain limited, small in scale and short in duration, with inconsistent effects on functional outcomes. Therefore, these findings should be interpreted with caution and cannot be considered conclusive evidence of therapeutic benefit. Further well-designed clinical trials are required to clarify the potential role of polyphenols as adjunctive strategies in chronic respiratory disease.