Therapeutic effects of flavonoids on pulmonary fibrosis: A preclinical meta-analysis

Background: The efficacy of flavonoid supplementation in animal models of pulmonary fibrosis has been demonstrated. Purpose: We conducted a systematic review and meta-analysis to evaluate the efficacy and underlying mechanisms of flavonoids in animal models of bleomycin-induced pulmonary fibrosis. Study design: Relevant studies (n = 45) were identified from English- and Chinese-language databases from the inception of the database until October 2023. Methods: Methodological quality was evaluated using the SYRCLE risk of bias tool. Statistical analyses were conducted using RevMan 5.3 and Stata 17.0. Lung inflammation and fibrosis score were the primary outcome indicators. Results: Flavonoids can alleviate pathological changes in the lungs. The beneficial effects of flavonoids on pulmonary fibrosis likely relate to their inhibition of inflammatory responses, restoration of oxidative and antioxidant homeostasis, and regulation of fibroblast proliferation, migration, and activation by transforming growth factor fi1/mothers against the decapentaplegic homologue/AMP-activated protein kinase (TGF-fi1/Smad3/ AMPK), inhibitor kappa B alpha/nuclear factor-kappa B (I kappa B alpha/NF-kappa B), phosphatidylinositol 3-kinase (PI3K)/ AKT, interleukin 6/signal transducer/activator of transcription 3 (IL6/STAT3), and nuclear factor erythroid 2related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathways. Conclusion: Flavonoids are potential candidate compounds for the prevention and treatment of pulmonary fibrosis. However, extensive preclinical research is necessary to confirm the antifibrotic properties of natural flavonoids.