Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice.
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.
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Daniela
D
Impellizzeri
2Department of Pharmacology, Faculty of Pharmacy,University of Seville,41012 Seville,Spain.
Elena
E
Talero
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Rosalba
R
Siracusa
2Department of Pharmacology, Faculty of Pharmacy,University of Seville,41012 Seville,Spain.
Antonio
A
Alcaide
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Marika
M
Cordaro
3PoliNat Inc.,35259 Ingenio,Las Palmas,Canary Islands,Spain.
Jose
J
Maria Zubelia
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Giuseppe
G
Bruschetta
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Rosalia
R
Crupi
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Emanuela
E
Esposito
1Department of Biological and Environmental Sciences,University of Messina,98166 Messina,Italy.
Salvatore
S
Cuzzocrea
2Department of Pharmacology, Faculty of Pharmacy,University of Seville,41012 Seville,Spain.
Virginia
V
Motilva
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis / Q000627:therapeutic use*; D000975:Antioxidants / Q000032:analysis / Q000627:therapeutic use*; D017209:Apoptosis; D019587:Dietary Supplements; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D031022:Mangifera / Q000737:chemistry; D008813:Mice, Inbred ICR; D020556:Neutrophil Infiltration; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D059808:Polyphenols / Q000032:analysis / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011794:Quercetin / Q000031:analogs & derivatives / Q000032:analysis / Q000627:therapeutic use; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use; D027843:Vitis / Q000737:chemistry; D044004:Xanthones / Q000032:analysis / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D010936:Plant Extracts; D059808:Polyphenols; D013267:Stilbenes; D044004:Xanthones; C013592:mangiferin; D011794:Quercetin; C003377:taxifolin; D000077185:Resveratrol
Apoptosis; BAL bronchoalveolar lavage; BLM bleomycin; COX-2 cyclo-oxygenase-2; DHQ dihydroquercetin; IPF idiopathic pulmonary fibrosis; Inflammation; Lung injury; MPO myeloperoxidase; Oxidative stress; PARP poly (ADP-ribose) polymerase; Polyphenols; ROS reactive oxygen species; iNOS inducible NO synthase; pERK phosphorylated extracellular signal-regulated kinase