Polyphenols have been described to have a wide range of
biological activities, and many reports, published during recent years, have highlighted the beneficial effects of phenolic compounds, illustrating their promising role as therapeutic tools in several acute and chronic disorders. The purpose of study was to evaluate, in an already-assessed model of
lung injury caused by
bleomycin (BLM) administration, the role of
resveratrol and
quercetin, as well as to explore the potential beneficial properties of a mango leaf extract, rich in
mangiferin, and a grape leaf extract, rich in
dihydroquercetin (DHQ), on the same model. Mice were subjected to intra-tracheal administration of BLM, and
polyphenols were administered by oral route immediately after BLM instillation and daily for 7 d. Treatment with
resveratrol,
mangiferin,
quercetin and DHQ inhibited oedema formation and
body weight loss, as well as ameliorated polymorphonuclear infiltration into the lung tissue and reduced the number of inflammatory cells in bronchoalveolar lavage fluid. Moreover,
polyphenols suppressed
inducible nitric oxide synthase expression, and prevented oxidative and nitroxidative
lung injury, as shown by the reduced
nitrotyrosine and
poly (ADP-ribose) polymerase levels. The degree of apoptosis, as evaluated by Bid and Bcl-2 balance, was also suppressed after
polyphenol treatment. Finally, these natural products down-regulated cyclo-oxygenase-2,
extracellular signal-regulated kinase phosphorylated expression and reduced NF-κBp65 translocation. Our findings confirmed the anti-inflammatory effects of
resveratrol and
quercetin in BLM-induced lung damage, and highlight, for the first time, the protective properties of exogenous administration of
mangiferin and DHQ on experimental
pulmonary fibrosis.