Abstract
Pulmonary fibrosis (PF) is a fatal chronic disease characterized by progressive interstitial scarring, alveolar destruction and a persistent decline in lung function. The present study evaluated the therapeutic effects of quercetin, a natural flavonoid with potent antioxidant and anti-inflammatory properties, in animal models of PF (PROSPERO registration no. INPLASY202530122). A comprehensive literature search was performed across PubMed, Web of Science, Embase, Cochrane Library and Ovid from inception to January 2025, identifying 25 eligible preclinical studies. Data were extracted and analyzed for outcomes in three main categories: Fibrotic changes, inflammatory responses and oxidative stress parameters. Random-effects meta-analysis was employed, followed by meta-regression analysis to examine study heterogeneity. The analysis indicated that quercetin administration was associated with improvements in fibrotic indicators, showing reduced collagen deposition and improved histopathological scores. Anti-inflammatory effects were observed through modulation of cytokine levels and inflammatory cell infiltration. Additionally, quercetin demonstrated effects on oxidative stress markers, showing enhanced antioxidant capacity and reduced oxidative damage. Meta-regression analysis identified a number of moderating factors, including dosage, treatment duration, animal model selection and induction method, which contributed to heterogeneity across studies. The findings suggest that quercetin may provide beneficial effects in experimental PF models through multiple pathways. However, notable heterogeneity was observed among included studies, indicating the need for cautious interpretation of results. Further investigation with standardized protocols is recommended to validate these preliminary findings.